http://www.mdpi.com/journal/nutrients Latest open access articles published in Nutrients at http://www.mdpi.com/journal/nutrients http://www.mdpi.com/2072-6643/5/6/2206 Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which may allow an avenue for improved treatment and support of patients suffering from hematologic disorders. In this review, we will summarize the role of vitamin D in normal hematopoiesis, discuss ways in which vitamin D may improve outcomes, and discuss a potential role of vitamin D for treating hematologic disorders and modulating the immune system to improve the outcome of allogeneic stem cell transplant. Nutrients 2013-06-18 5 6 Review 10.3390/nu5062206 2206 2221 2072-6643 2013-06-18 doi: 10.3390/nu5062206 Aric Hall Mark Juckett http://www.mdpi.com/2072-6643/5/6/2192 White matter lesions have detrimental effects upon older adults, while serum calcium levels have been associated with elevated vascular risk and may be associated with these lesions. Depression, a serious mental disorder characterized by disturbances in calcium metabolism, may be an important contributor to any calcium-lesion relationship. This cross-sectional pilot study examined the association between serum ionized calcium (the physiologically active form of calcium) and white matter lesion volumes in a sample of depressed and non-depressed older adults (N = 42; 60 years and older). Serum ionized calcium was determined using an ion-selective electrode technique, while lesion volumes were estimated from magnetic resonance imaging using an automated expectation-maximization segmentation. A linear regression model, controlling for age and group (depression vs. comparison), showed a trend for a positive relationship between serum ionized calcium and white matter lesion volume (β = 4.34, SE = 2.27, t = 1.91, p = 0.063). Subsample analyses with depressed participants showed a significant positive relationship between higher ionic calcium and greater lesion volume (β = 6.41, SE = 2.53, t = 2.53, p = 0.018), but no association was found for non-depressed participants. Sex-specific subsample analyses showed a significant positive relationship between higher calcium and greater lesion volume in men only (β = 7.49, SE = 3.42, t = 2.19, p = 0.041). These preliminary results indicate that serum ionized calcium may be associated with white matter lesions in older adults, particularly among men and individuals with depression. Larger studies are needed to confirm these findings. Nutrients 2013-06-18 5 6 Article 10.3390/nu5062192 2192 2205 2072-6643 2013-06-18 doi: 10.3390/nu5062192 Martha Payne Cortnee Pierce Douglas McQuoid David Steffens John Anderson http://www.mdpi.com/2072-6643/5/6/2173 Oral cancer represents a health burden worldwide with approximate 275,000 new cases diagnosed annually. Its poor prognosis is due to local tumor invasion and frequent lymph node metastasis. Better understanding and development of novel treatments and chemo-preventive approaches for the preventive and therapeutic intervention of this type of cancer are necessary. Recent development of dietary polyphenols as cancer preventives and therapeutic agents is of great interest due to their antioxidant and anti-carcinogenic activities. Polyphenols may inhibit carcinogenesis in the stage of initiation, promotion, or progression. In particular, dietary polyphenols decrease incidence of carcinomas and exert protection against oral cancer by induction of cell death and inhibition of tumor growth, invasion, and metastasis. In this review, we discuss current progress of dietary polyphenols against oral cancers in vitro, in vivo, and at population levels. Nutrients 2013-06-14 5 6 Review 10.3390/nu5062173 2173 2191 2072-6643 2013-06-14 doi: 10.3390/nu5062173 Yijian Ding Hua Yao Yanan Yao Leonard Fai Zhuo Zhang http://www.mdpi.com/2072-6643/5/6/2144 This study investigated if additional non-starch polysaccharide (NSP) or resistant starch (RS), above that currently recommended, leads to better improvement in insulin sensitivity (IS) than observed with modest weight loss (WL). Obese male volunteers (n = 14) were given an energy-maintenance (M) diet containing 27 g NSP and 5 g RS daily for one week. They then received, in a cross-over design, energy-maintenance intakes of either an NSP-enriched diet (42 g NSP, 2.5 g RS) or an RS-enriched diet (16 g NSP, 25 g RS), each for three weeks. Finally, a high protein (30% calories) WL diet was provided at 8 MJ/day for three weeks. During each dietary intervention, endogenous glucose production (EGP) and IS were assessed. Fasting glycaemia was unaltered by diet, but plasma insulin and C-peptide both decreased with the WL diet (p < 0.001), as did EGP (−11%, p = 0.006). Homeostatis model assessment of insulin resistance improved following both WL (p < 0.001) and RS (p < 0.05) diets. Peripheral tissue IS improved only with WL (57%–83%, p < 0.005). Inclusion of additional RS or NSP above amounts currently recommended resulted in little or no improvement in glycaemic control, whereas moderate WL (approximately 3 kg fat) improved IS. Nutrients 2013-06-10 5 6 Article 10.3390/nu5062144 2144 2172 2072-6643 2013-06-10 doi: 10.3390/nu5062144 Gerald Lobley Grietje Holtrop David Bremner A. Calder Eric Milne Alexandra Johnstone http://www.mdpi.com/2072-6643/5/6/2128 Asthma is a chronic disease, characterized by airway inflammation, airflow limitation, hyper-reactivity and airway remodeling. It is believed that asthma is caused by the interaction between genetic and environmental factors. The prevalence of allergic diseases, including asthma, has increased worldwide during the past two decades. Although the precise reasons that have caused this increase remain unknown, dietary change is thought to be one of the environmental factors. Flavonoids, which are polyphenolic plant secondary metabolites ubiquitously present in vegetables, fruits and beverages, possess antioxidant and anti-allergic traits, as well as immune-modulating activities. Flavonoids are powerful antioxidants and anti-allergic nutrients that inhibit the release of chemical mediators, synthesis of Th2 type cytokines, such as interleukin (IL)-4 and IL-13, and CD40 ligand expression by high-affinity immunoglobulin E (IgE) receptor-expressing cells, such as mast cells and basophils. They also inhibit IL-4-induced signal transduction and affect the differentiation of naïve CD4+ T cells into effector T-cells through their inhibitory effect on the activation of the aryl hydrocarbon receptor. Various studies of flavonoids in asthmatic animal models have demonstrated their beneficial effects. The results of several epidemiological studies suggest that an increase in flavonoid intake is beneficial for asthma. Moreover, clinical trials of flavonoids have shown their ameliorative effects on symptoms related to asthma. However, these human studies are currently limited; further validation is required to clarify whether an appropriate intake of flavonoids may constitute dietary treatment and for part of a preventive strategy for asthma. Nutrients 2013-06-10 5 6 Review 10.3390/nu5062128 2128 2143 2072-6643 2013-06-10 doi: 10.3390/nu5062128 Toshio Tanaka Ryo Takahashi http://www.mdpi.com/2072-6643/5/6/2114 Vitamin D deficiency (≤50nmol/L 25-hydroxy vitamin D) is a cardiovascular (CV) risk factor that affects approximately one billion people worldwide, particularly those affected by chronic kidney disease (CKD). Individuals with CKD demonstrate abnormal cardiac autonomic nervous system activity, which has been linked to the significant rates of CV-related mortality in this population. Whether vitamin D deficiency has a direct association with regulation of cardiac autonomic activity has never been explored in humans. Methods: Thirty-four (34) healthy, normotensive subjects were studied and categorized based on 25-hydroxy vitamin D deficiency (deficient vs. non-deficient, n = 7 vs. 27), as well as 1,25-dihydroxy vitamin D levels (above vs. below 25th percentile, n = 8 vs. 26). Power spectral analysis of electrocardiogram recordings provided measures of cardiac autonomic activity across low frequency (LF) and high frequency (HF, representative of vagal contribution) bands, representative of the sympathetic and vagal limbs of the autonomic nervous system when transformed to normalized units (nu), respectively, as well as overall cardiosympathovagal balance (LF:HF) during graded angiotensin II (AngII) challenge (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min). Results: At baseline, significant suppression of sympathovagal balance was observed in the 25-hydroxy vitamin D-deficient participants (LF:HF, p = 0.02 vs. non-deficient), although no other differences were observed throughout AngII challenge. Participants in the lowest 1,25-dihydroxy VD quartile experienced significant withdrawal of inhibitory vagal control, as well as altered overall sympathovagal balance throughout AngII challenge (HF, mean difference = −6.98 ± 3 nu, p = 0.05; LF:HF, mean difference = 0.34 ± 0.1, p = 0.043 vs. above 25th percentile). Conclusions: Vitamin D deficiency is associated with suppression of resting cardiac autonomic activity, while low 1,25-dihydroxy vitamin D levels are associated with unfavourable cardiac autonomic activity during an acute AngII stressor, offering a potential pathophysiological mechanism that may be acting to elevate CV risk in in populations with low vitamin D status. Nutrients 2013-06-10 5 6 Article 10.3390/nu5062114 2114 2127 2072-6643 2013-06-10 doi: 10.3390/nu5062114 Michelle Mann Derek Exner Brenda Hemmelgarn Darlene Sola Tanvir Turin Linda Ellis Sofia Ahmed http://www.mdpi.com/2072-6643/5/6/2093 Dietary fiber may contribute to satiety. This study examined the effect of two dietary fiber characteristics, small intestinal contents viscosity and large intestinal fermentability, on satiety-and adiposity-related hormones in rats. Diets contained fiber sources that were non-viscous, somewhat viscous, or highly viscous, and either highly fermentable or non-fermentable, in a 2 × 3 factorial design. In the fed state (2 h postprandial), rats fed non-fermentable fibers had significantly greater plasma GLP-1 concentration than fermentable fibers. In the fasted state, among non-fermentable fibers, viscosity had no effect on GLP-1 concentration. However, among fermentable fibers, greater viscosity reduced GLP-1 concentration. Plasma peptide tyrosine tyrosine (PYY) concentrations in the fasted state were not influenced by the fermentability of the fiber overall, however animals consuming a fructooligosaccharide greater PYY concentration. In both the fed and fasted states, rats fed non-fermentable fibers had a significantly lower plasma ghrelin concentration than rats fed fermentable fibers. In the fasted state, rats fed non-fermentable fibers had a significantly lower plasma leptin concentration than rats fed fermentable fibers. Thus, fermentability and viscosity of dietary fiber interacted in complex ways to influence satiety- and adiposity-related plasma hormone concentrations. However, the results suggest that highly viscous, non-fermentable fibers may limit weight gain and reduce adiposity and non-fermentable fibers, regardless of viscosity, may promote meal termination. Nutrients 2013-06-07 5 6 Article 10.3390/nu5062093 2093 2113 2072-6643 2013-06-07 doi: 10.3390/nu5062093 Natalia Schroeder Len Marquart Daniel Gallaher http://www.mdpi.com/2072-6643/5/6/2076 Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification. Nutrients 2013-06-07 5 6 Article 10.3390/nu5062076 2076 2092 2072-6643 2013-06-07 doi: 10.3390/nu5062076 Stefania Pacini Gabriele Morucci Jacopo Branca Stefano Aterini Marcello Amato Massimo Gulisano Marco Ruggiero http://www.mdpi.com/2072-6643/5/6/2062 An emerging trend in sports nutrition is the consumption of energy drinks and “energy shots”. Energy shots may prove to be a viable pre-competition supplement for runners. Six male runners (mean ± SD age and VO2max: 22.5 ± 1.8 years and 69.1 ± 5.7 mL·kg−1·min−1) completed three trials [placebo (PLA; 0 mg caffeine), Guayakí Yerba Maté Organic Energy Shot™ (YM; 140 mg caffeine), or Red Bull Energy Shot™ (RB; 80 mg caffeine)]. Treatments were ingested following a randomized, placebo-controlled crossover design. Participants ran a five kilometer time trial on a treadmill. No differences (p > 0.05) in performance were detected with RB (17.55 ± 1.01 min) or YM ingestion (17.86 ± 1.59 min) compared to placebo (17.44 ± 1.25 min). Overall, energy shot ingestion did not improve time-trial running performance in trained runners. Nutrients 2013-06-06 5 6 Article 10.3390/nu5062062 2062 2075 2072-6643 2013-06-06 doi: 10.3390/nu5062062 Matthew Schubert Todd Astorino John Jr. http://www.mdpi.com/2072-6643/5/6/2047 Obesity and osteoporosis are important global health problems characterized by increasing prevalence with high impact on morbidity and mortality. The objective of this review was to determine whether excess weight during adolescence interferes with bone mass accumulation. If bone mineral gain can be optimized during puberty, adults are less likely to suffer from the devastating complications of osteoporosis. The increased fracture risk in obese children has also been attributed to a lower bone mass for weight compared to non-obese children. Thus, adiposity present in this age group may not result in the protection of bone mass, in contrast to what has been observed in adults. However, studies involving adolescents have reported both protective and detrimental effects of obesity on bone. The results and mechanisms of these interactions are controversial and have not been fully elucidated, a fact highlighting the extreme relevance of this topic and the need to monitor intervening and interactive variables. Nutrients 2013-06-06 5 6 Review 10.3390/nu5062047 2047 2061 2072-6643 2013-06-06 doi: 10.3390/nu5062047 Luciana Mosca Valéria da Silva Tamara Goldberg http://www.mdpi.com/2072-6643/5/6/2028 Food allergies are one of the first manifestations of allergic disease and have been shown to significantly impact on general health perception, parental emotional distress and family activities. It is estimated that in the Western world, almost one in ten children have an IgE-mediated allergy. Cow’s milk and egg allergy are common childhood allergies. Until recently, children with food allergy were advised to avoid all dietary exposure to the allergen to which they were sensitive, in the thought that consumption would exacerbate their allergy. However, recent publications indicate that up to 70% of children with egg allergy can tolerate egg baked in a cake or muffin without apparent reaction. Likewise, up to 75% of children can tolerate baked goods containing cow’s milk, and these children demonstrate IgE and IgG4 profiles indicative of tolerance development. This article will review the current literature regarding the use of heated food allergens as immunotherapy for children with cow’s milk and egg allergy. Nutrients 2013-06-05 5 6 Review 10.3390/nu5062028 2028 2046 2072-6643 2013-06-05 doi: 10.3390/nu5062028 Merryn Netting Maria Makrides Michael Gold Patrick Quinn Irmeli Penttila http://www.mdpi.com/2072-6643/5/6/2019 The burden of obesity has increased globally over the last few decades and its association with insulin resistance and related cardio-metabolic problems have adversely affected our ability to reduce population morbidity and mortality. Traditionally, adipose tissue in the visceral fat depot has been considered a major culprit in the development of insulin resistance. However, there is a growing body of evidence supporting the role of subcutaneous truncal/abdominal adipose tissue in the development of insulin resistance. There are significant differences in the functional characteristics of subcutaneous abdominal/truncal vs. intraabdominal vs. gluteo-femoral fat depots. More recently, mounting evidence has been supporting the role of adipose tissue function in the development of metabolic complications independent of adipose tissue volume or distribution. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger a vicious cycle of inflammation leading to subcutaneous adipose tissue dysfunction and ectopic fat deposition. Therapeutic lifestyle change continues to be the most important intervention in clinical practice to improve adipose tissue function and avoid development of insulin resistance and related cardio-metabolic complications. Nutrients 2013-06-05 5 6 Review 10.3390/nu5062019 2019 2027 2072-6643 2013-06-05 doi: 10.3390/nu5062019 Pavankumar Patel Nicola Abate http://www.mdpi.com/2072-6643/5/6/2006 Parenteral nutrition (PN) is a feeding mode suitable for children that do not achieve requirements via the enteral route. For this intervention to be successful, healthcare professionals require: knowledge on nutrient requirements; access to an aseptic compounding facility; and a system that ensures adequate and safe delivery of PN. Previously, it was thought that individualised PN was the “gold standard” for delivering nutrients to children; however, studies have highlighted concerns regarding inadequate delivery of nutrients, prescribing and compounding errors. We, therefore, set out to develop and implement all-in-one (AIO) paediatric PN solutions. Through a systematic approach, four AIO PN solutions were developed: birth–two months of age (Ped 1); two months–10 kg (Ped 2); 11–15 kg (Ped 3); and 16–30 kg (Ped 4). We implemented them with the help of a teaching pack, over a one month time period, and reviewed usage at six months. At that time, five children initially received standard PN without electrolyte changes; but after a few days, electrolytes needed amendments, and three required individualised PN. A change to AIO PN is feasible and safe; however, some may require electrolyte changes, and there will always be those that will require individualised PN. Nutrients 2013-06-05 5 6 Article 10.3390/nu5062006 2006 2018 2072-6643 2013-06-05 doi: 10.3390/nu5062006 Rosan Meyer Meike Timmermann Sven Schulzke Caroline Kiss Marc Sidler Raoul Furlano http://www.mdpi.com/2072-6643/5/6/1989 Purpose: Rare spontaneous remissions from age-related macular degeneration (AMD) suggest the human retina has large regenerative capacity, even in advanced age. We present examples of robust improvement of retinal structure and function using an OTC oral resveratrol (RV) based nutritional supplement called Longevinex® or L/RV (circa 2004, Resveratrol Partners, LLC, Las Vegas, NV, USA). RV, a polyphenolic phytoalexin caloric-restriction mimic, induces hormesis at low doses with widespread beneficial effects on systemic health. RV alone inhibits neovascularization in the murine retina. Thus far, published evidence includes L/RV mitigation of experimentally induced murine cardiovascular reperfusion injury, amelioration of human atherosclerosis serum biomarkers in a human Japanese randomized placebo controlled trial, modulation of micro RNA 20b and 539 that control hypoxia-inducing-factor (HIF-1) and vascular endothelial growth factor (VEGF) genes in the murine heart (RV inhibited micro RNA20b 189-fold, L/RV 1366-fold). Little is known about the effects of L/RV on human ocular pathology. Methods: Absent FDA IRB approval, but with permission from our Chief of Staff and medical center IRB, L/RV is reserved for AMD patients, on a case-by-case compassionate care basis. Patients include those who progress on AREDS II type supplements, refuse intra-vitreal anti-VEGF injections or fail to respond to Lucentis®, Avastin® or Eylea®. Patients are clinically followed traditionally as well as with multi-spectral retinal imaging, visual acuity, contrast sensitivity, cone glare recovery and macular visual fields. Three cases are presented. Results: Observed dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with a suggestion of improvement in choroidal blood flow by near IR multispectral imaging. The visual function improvement mirrors the effect seen anatomically. The effect is bilateral with the added benefit of better RPE function. Effects have lasted for one year or longer when taken daily, at which point one patient required initiation of anti-VEGF agents. Unanticipated systemic benefits were observed. Conclusions: Preliminary observations support previous publications in animals and humans. Restoration of structure and visual function in octogenarians with daily oral consumption of L/RV is documented. Applications include failure on AREDS II supplements, refusing or failing conventional anti-VEGF therapy, adjunct therapy to improve RPE function, and compassionate use in medically underserved or economically depressed third-world countries. Nutrients 2013-06-04 5 6 Case Report 10.3390/nu5061989 1989 2005 2072-6643 2013-06-04 doi: 10.3390/nu5061989 Stuart Richer William Stiles Lawrence Ulanski Donn Carroll Carla Podella http://www.mdpi.com/2072-6643/5/6/1970 High-producing ruminants are fed high amounts of cereal grains, at the expense of dietary fiber, to meet their high energy demands. Grains consist mainly of starch, which is easily degraded in the rumen by microbial glycosidases, providing energy for rapid growth of rumen microbes and short-chain fatty acids (SCFA) as the main energy source for the host. Yet, low dietary fiber contents and the rapid accumulation of SCFA lead to rumen disorders in cattle. The chemical processing of grains has become increasingly important to confer their starch resistances against rumen microbial glycosidases, hence generating ruminally resistant starch (RRS). In ruminants, unlike monogastric species, the strategy of enhancing resistant starch is useful, not only in lowering the amount of carbohydrate substrates available for digestion in the upper gut sections, but also in enhancing the net hepatic glucose supply, which can be utilized by the host more efficiently than the hepatic gluconeogenesis of SCFA. The use of chemical methods to enhance the RRS of grains and the feeding of RRS face challenges in the practice; therefore, the present article attempts to summarize the most important achievements in the chemical processing methods used to generate RRS, and review advantages and challenges of feeding RRS to ruminants Nutrients 2013-06-04 5 6 Review 10.3390/nu5061970 1970 1988 2072-6643 2013-06-04 doi: 10.3390/nu5061970 Kathrin Deckardt Annabella Khol-Parisini Qendrim Zebeli http://www.mdpi.com/2072-6643/5/6/1962 Three dietary carotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the central retina (macula), where they are collectively referred to as macular pigment (MP). MP’s pre-receptoral absorption of blue light and consequential attenuation of the effects of chromatic aberration and light scatter are important for optimal visual function. Furthermore, antioxidant activity of MP’s constituent carotenoids and the same blue light-filtering properties underlie the rationale for its putative protective role for age-related macular degeneration (AMD). Supplementation with L, Z and MZ augments MP and enhances visual performance in diseased and non-diseased eyes, and may reduce risk of AMD development and/or progression. Nutrients 2013-05-29 5 6 Article 10.3390/nu5061962 1962 1969 2072-6643 2013-05-29 doi: 10.3390/nu5061962 Ekaterina Loskutova John Nolan Alan Howard Stephen Beatty http://www.mdpi.com/2072-6643/5/6/1949 Natural killer (NK) cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA) and eicosapentaenoic (EPA) acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA) on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day) or DHA (240 mg/kg BW/day) were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG) E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats. Nutrients 2013-05-29 5 6 Article 10.3390/nu5061949 1949 1961 2072-6643 2013-05-29 doi: 10.3390/nu5061949 Sachiko Juman Michio Hashimoto Masanori Katakura Takayuki Inoue Yoko Tanabe Makoto Arita Tomohiro Miki Osamu Shido http://www.mdpi.com/2072-6643/5/6/1937 Selenium is an essential trace element in the diet of mammals which is important for many physiological functions. However, a number of epidemiological studies have suggested that high selenium status is a possible risk factor for the development of type 2 diabetes, although they cannot distinguish between cause and effect. Selenoprotein P (Sepp1) is central to selenium homeostasis and widely expressed in the organism. Here we review the interaction between Sepp1 and glucose metabolism with an emphasis on experimental evidence. In models with or without gene modification, glucose and insulin can regulate Sepp1 expression in the pancreas and liver, and vice versa. Especially in the liver, Sepp1 is regulated virtually like a gluconeogenic enzyme. Combining these data suggests that there could be a feedback regulation between hepatic Sepp1 and pancreatic insulin and that increasing circulating Sepp1 might be the result rather than the cause of abnormal glucose metabolism. Future studies specifically designed to overexpress Sepp1 are needed in order to provide a more robust link between Sepp1 and type 2 diabetes. Nutrients 2013-05-29 5 6 Review 10.3390/nu5061937 1937 1948 2072-6643 2013-05-29 doi: 10.3390/nu5061937 Jinyuan Mao Weiping Teng http://www.mdpi.com/2072-6643/5/6/1913 The elderly chronic kidney disease (CKD) population is growing. Both aging and CKD can disrupt calcium (Ca2+) homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD). CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD. Nutrients 2013-05-29 5 6 Review 10.3390/nu5061913 1913 1936 2072-6643 2013-05-29 doi: 10.3390/nu5061913 Vickram Tejwani Qi Qian http://www.mdpi.com/2072-6643/5/6/1869 Probiotics are beneficial microbes that confer a realistic health benefit on the host, which in combination with prebiotics, (indigestible dietary fibre/carbohydrate), also confer a health benefit on the host via products resulting from anaerobic fermentation. There is a growing body of evidence documenting the immune-modulatory ability of probiotic bacteria, it is therefore reasonable to suggest that this is potentiated via a combination of prebiotics and probiotics as a symbiotic mix. The need for probiotic formulations has been appreciated for the health benefits in “topping up your good bacteria” or indeed in an attempt to normalise the dysbiotic microbiota associated with immunopathology. This review will focus on the immunomodulatory role of probiotics and prebiotics on the cells, molecules and immune responses in the gut mucosae, from epithelial barrier to priming of adaptive responses by antigen presenting cells: immune fate decision—tolerance or activation? Modulation of normal homeostatic mechanisms, coupled with findings from probiotic and prebiotic delivery in pathological studies, will highlight the role for these xenobiotics in dysbiosis associated with immunopathology in the context of inflammatory bowel disease, colorectal cancer and hypersensitivity. Nutrients 2013-05-29 5 6 Review 10.3390/nu5061869 1869 1912 2072-6643 2013-05-29 doi: 10.3390/nu5061869 Holly Hardy Jennifer Harris Eleanor Lyon Jane Beal Andrew Foey http://www.mdpi.com/2072-6643/5/6/1856 Vitamin D is well known for its role in calcium regulation and bone health, but emerging literature tells of vitamin D’s central role in other vital body processes, such as: signaling gene response, protein synthesis, hormone synthesis, immune response, plus, cell turnover and regeneration. The discovery of the vitamin D receptor within the muscle suggested a significant role for vitamin D in muscle tissue function. This discovery led researchers to question the impact that vitamin D deficiency could have on athletic performance and injury. With over 77% of the general population considered vitamin D insufficient, it’s likely that many athletes fall into the same category. Research has suggested vitamin D to have a significant effect on muscle weakness, pain, balance, and fractures in the aging population; still, the athletic population is yet to be fully examined. There are few studies to date that have examined the relationship between vitamin D status and performance, therefore, this review will focus on the bodily roles of vitamin D, recommended 25(OH)D levels, vitamin D intake guidelines and risk factors for vitamin D insufficiency in athletes. In addition, the preliminary findings regarding vitamin D’s impact on athletic performance will be examined. Nutrients 2013-05-28 5 6 Review 10.3390/nu5061856 1856 1868 2072-6643 2013-05-28 doi: 10.3390/nu5061856 Dana Ogan Kelly Pritchett http://www.mdpi.com/2072-6643/5/6/1840 Sodium intakes, from foods and beverages, of 22,852 persons in the National Health and Nutrition Examination Surveys (NHANES 2003–2008) were examined by specific food source and by food location of origin. Analyses were based on a single 24-h recall. Separate analyses were conducted for children (6–11 years of age), adolescents (12–19), and adults (20–50 and ≥51 years). Grouping of like foods (e.g., food sources) used a scheme proposed by the National Cancer Institute, which divides foods/beverages into 96 food subgroups (e.g., pizza, yeast breads or cold cuts). Food locations of origin were stores (e.g., grocery, convenience and specialty stores), quick-service restaurant/pizza (QSR), full-service restaurant (FSR), school, or other. Food locations of sodium were also evaluated by race/ethnicity amongst adults. Stores provided between 58.1% and 65.2% of dietary sodium, whereas QSR and FSR together provided between 18.9% and 31.8% depending on age. The proportion of sodium from QSR varied from 10.1% to 19.9%, whereas that from FSR varied from 3.4% to 13.3%. School meals provided 10.4% of sodium for 6–11 year olds and 6.0% for 12–19 year olds. Pizza from QSR, the top away from home food item, provided 5.4% of sodium in adolescents. QSR pizza, chicken, burgers and Mexican dishes combined provided 7.8% of total sodium in adult diets. Most sodium came from foods purchased in stores. Food manufacturers, restaurants, and grocery stores all have a role to play in reducing the amount of sodium in the American diet. Nutrients 2013-05-28 5 6 Article 10.3390/nu5061840 1840 1855 2072-6643 2013-05-28 doi: 10.3390/nu5061840 Adam Drewnowski Colin Rehm http://www.mdpi.com/2072-6643/5/5/1823 The lens and retina of the human eye are exposed constantly to light and oxygen. In situ phototransduction and oxidative phosphorylation within photoreceptors produces a high level of phototoxic and oxidative related stress. Within the eye, the carotenoids lutein and zeaxanthin are present in high concentrations in contrast to other human tissues. We discuss the role of lutein and zeaxanthin in ameliorating light and oxygen damage, and preventing age-related cellular and tissue deterioration in the eye. Epidemiologic research shows an inverse association between levels of lutein and zeaxanthin in eye tissues and age related degenerative diseases such as macular degeneration (AMD) and cataracts. We examine the role of these carotenoids as blockers of blue-light damage and quenchers of oxygen free radicals. This article provides a review of possible mechanisms of lutein action at a cellular and molecular level. Our review offers insight into current clinical trials and experimental animal studies involving lutein, and possible role of nutritional intervention in common ocular diseases that cause blindness. Nutrients 2013-05-22 5 5 Review 10.3390/nu5051823 1823 1839 2072-6643 2013-05-22 doi: 10.3390/nu5051823 Keyvan Koushan Raluca Rusovici Wenhua Li Lee Ferguson Kakarla Chalam http://www.mdpi.com/2072-6643/5/5/1801 Functional innate and acquired immune responses are required to protect the host from pathogenic bacterial infections. Modulation of host immune functions may have beneficial or deleterious effects on disease outcome. Different types of dietary fatty acids have been shown to have variable effects on bacterial clearance and disease outcome through suppression or activation of immune responses. Therefore, we have chosen to review research across experimental models and food sources on the effects of commonly consumed fatty acids on the most common food-borne pathogens, including Salmonella sp., Campylobacter sp., Shiga toxin-producing Escherichia coli, Shigella sp., Listeria monocytogenes, and Staphylococcus aureus. Altogether, the compilation of literature suggests that no single fatty acid is an answer for protection from all food-borne pathogens, and further research is necessary to determine the best approach to improve disease outcomes. Nutrients 2013-05-22 5 5 Review 10.3390/nu5051801 1801 1822 2072-6643 2013-05-22 doi: 10.3390/nu5051801 Lisa Harrison Kannan Balan Uma Babu http://www.mdpi.com/2072-6643/5/5/1757 Diarrhoea is a common disease which causes pain and may be deadly, especially in developing countries. In Bangladesh, diarrhoeal diseases affect thousands of people every year, and children are especially vulnerable. Bacterial toxins or viral infections are the most common cause of the disease. The diarrhoea outbreaks are often associated with flood affected areas with contaminated drinking water and an increased risk of spreading the water-borne disease. Not surprisingly, plants found in the near surroundings have been taken into use by the local community as medicine to treat diarrhoeal symptoms. These plants are cheaper and more easily available than conventional medicine. Our question is: What is the level of documentation supporting the use of these plants against diarrhoea and is their consumption safe? Do any of these plants have potential for further exploration? In this review, we have choosen seven plant species that are used in the treatment of diarrhoea; Diospyros peregrina, Heritiera littoralis, Ixora coccinea, Pongamia pinnata, Rhizophora mucronata, Xylocarpus granatum, and Xylocarpus moluccensis. Appearance and geographical distribution, traditional uses, chemical composition, and biological studies related to antidiarrhoeal activity will be presented. This review reveals that there is limited scientific evidence supporting the traditional use of these plants. Most promising are the barks from D. peregrina, X. granatum and X. moluccensis which contain tannins and have shown promising results in antidiarrhoeal mice models. The leaves of P. pinnata also show potential. We suggest these plants should be exploited further as possible traditional herbal remedies against diarrhoea including studies on efficacy, optimal dosage and safety. Nutrients 2013-05-22 5 5 Review 10.3390/nu5051757 1757 1800 2072-6643 2013-05-22 doi: 10.3390/nu5051757 Helle Wangensteen Line Klarpås Mahiuddin Alamgir Anne Samuelsen Karl Malterud http://www.mdpi.com/2072-6643/5/5/1734 Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM). The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed. Nutrients 2013-05-21 5 5 Review 10.3390/nu5051734 1734 1756 2072-6643 2013-05-21 doi: 10.3390/nu5051734 Claire Weekley Jade Aitken Lydia Finney Stefan Vogt Paul Witting Hugh Harris http://www.mdpi.com/2072-6643/5/5/1719 Dietary intake among other lifestyle factors influence blood pressure. We examined the associations of an ―a priori‖ diet score with incident high normal blood pressure (HNBP; systolic blood pressure (SBP) 120–139 mmHg, or diastolic blood pressure (DBP) 80–89 mmHg and no antihypertensive medications) and hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or taking antihypertensive medication). We used proportional hazards regression to evaluate this score in quintiles (Q) and each food group making up the score relative to incident HNBP or hypertension over nine years in the Atherosclerosis Risk of Communities (ARIC) study of 9913 African-American and Caucasian adults aged 45–64 years and free of HNBP or hypertension at baseline. Incidence of HNBP varied from 42.5% in white women to 44.1% in black women; and incident hypertension from 26.1% in white women to 40.8% in black women. Adjusting for demographics and CVD risk factors, the ―a priori‖ food score was inversely associated with incident hypertension; but not HNBP. Compared to Q1, the relative hazards of hypertension for the food score Q2–Q5 were 0.97 (0.87–1.09), 0.91 (0.81–1.02), 0.91 (0.80–1.03), and 0.86 (0.75–0.98); ptrend = 0.01. This inverse relation was largely attributable to greater intake of dairy products and nuts, and less meat. These findings support the 2010 Dietary Guidelines to consume more dairy products and nuts, but suggest a reduction in meat intake. Nutrients 2013-05-21 5 5 Article 10.3390/nu5051719 1719 1733 2072-6643 2013-05-21 doi: 10.3390/nu5051719 Lu-Chen Weng Lyn Steffen Moyses Szklo Jennifer Nettleton Lloyd Chambless Aaron Folsom http://www.mdpi.com/2072-6643/5/5/1706 Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations. Nutrients 2013-05-21 5 5 Article 10.3390/nu5051706 1706 1718 2072-6643 2013-05-21 doi: 10.3390/nu5051706 Jian Gong Li Hsu Tabitha Harrison Irena King Stefan Stürup Xiaoling Song David Duggan Yan Liu Carolyn Hutter Stephen Chanock Charles Eaton James Marshall Ulrike Peters http://www.mdpi.com/2072-6643/5/5/1672 Obesity, a chronic low-grade inflammatory condition is associated with the development of many comorbidities including dyslipidemia. This review examines interactions between single nucleotide polymorphisms (SNP) in the inflammatory genes tumor necrosis alpha (TNFA) and interleukin-6 (IL-6) and dietary fatty acids, and their relationship with obesity and serum lipid levels. In summary, dietary fatty acids, in particular saturated fatty acids and the omega-3 and omega-6 polyunsaturated fatty acids, impact the expression of the cytokine genes TNFA and IL-6, and alter TNFα and IL-6 production. In addition, sequence variants in these genes have also been shown to alter their gene expression and plasma levels, and are associated with obesity, measures of adiposity and serum lipid concentrations. When interactions between dietary fatty acids and TNFA and IL-6 SNPs on obesity and serum lipid were analyzed, both the quantity and quality of dietary fatty acids modulated the relationship between TNFA and IL-6 SNPs on obesity and serum lipid profiles, thereby impacting the association between phenotype and genotype. Researching these diet–gene interactions more extensively, and understanding the role of ethnicity as a confounder in these relationships, may contribute to a better understanding of the inter-individual variability in the obese phenotype. Nutrients 2013-05-21 5 5 Review 10.3390/nu5051672 1672 1705 2072-6643 2013-05-21 doi: 10.3390/nu5051672 Yael Joffe Malcolm Collins Julia Goedecke http://www.mdpi.com/2072-6643/5/5/1660 Uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter that is expressed mainly in skeletal muscle where it plays an important role in energy expenditure and fat oxidation. In this study, we investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on UCP3 gene expression in C2C12 muscle cells. EPA and DHA up-regulated UCP3 mRNA level in a dose-dependent manner and similarly increased UCP3 promoter activity in C2C12 muscle cells. To determine whether AMP-activated protein kinase (AMPK) signaling may also directly regulate UCP3 expression, 5′-amino-4-imidazolecarboxamide-ribonucleoside (AICAR), an AMP analog that activates AMPK, was treated in C2C12 muscle cells. AICAR showed additive effects with EPA or DHA on the UCP3 promoter activation. These results indicate that EPA and DHA directly regulate the gene expression of UCP3, potentially through AMPK-mediated pathway in C2C12 muscle cells. Nutrients 2013-05-21 5 5 Article 10.3390/nu5051660 1660 1671 2072-6643 2013-05-21 doi: 10.3390/nu5051660 Mak-Soon Lee In-Hwan Kim Yangha Kim http://www.mdpi.com/2072-6643/5/5/1648 Atherosclerosis is a complicated progress, involving many types of cells. Although the exact mechanisms of progression of atherosclerosis are uncertain, the balance of vascular smooth muscle cells (VSMCs) proliferation and apoptosis appears to play a pivotal role in the pathogenesis and progression of atherosclerosis, and much discussion has been undertaken to elucidate the detailed mechanisms, relevant gene expression and transduction pathways. Drug treatment has focused on ameliorating atherosclerosis. Some researchers have indicated that inhibiting VSMCs proliferation is involved in attenuating atherosclerosis. Luteolin is a kind of flavonoids naturally occurring in many plants and possesses beneficial effects on cardiovascular diseases. Luteolin can reduce VSMCs’ proliferation and migration and this reduction is stimulated by several factors. The aim of this review is to summarize the existing inhibitory effects and mechanisms of luteolin on proliferation and migration of VSMCs, and consider whether luteolin may be a potential candidate for preventing and treating atherosclerosis. Nutrients 2013-05-17 5 5 Review 10.3390/nu5051648 1648 1659 2072-6643 2013-05-17 doi: 10.3390/nu5051648 Dehua Jiang Dongye Li Wanling Wu http://www.mdpi.com/2072-6643/5/5/1622 The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import), the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export) and the role of ferritin in the process of iron acquisition (iron storage). We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration. Nutrients 2013-05-17 5 5 Review 10.3390/nu5051622 1622 1647 2072-6643 2013-05-17 doi: 10.3390/nu5051622 Konstantinos Mandilaras Tharse Pathmanathan Fanis Missirlis http://www.mdpi.com/2072-6643/5/5/1609 Vitamin A is essential for growth and development. We investigated whether high consumption of energy-dense nutrient-poor foods in the diets of pre-school children is detrimental to diet quality with respect to vitamin A. Data were collected from 755 children at 18-months and 3½-years, from the Avon Longitudinal Study of Parents and Children, using 3-day unweighed dietary records completed by parents in 1994 and 1996, respectively. Energy, carotene and retinol intakes were calculated. The quality of the diet declined from 18-months to 3½-years with respect to vitamin A. Preformed retinol intakes decreased by −54 μg/day on average (p = 0.003). Carotene intakes were similar at each age although there was a 23% increase in energy intake by 3½-years. Longitudinally those in the highest quartile of intake at 18-months were twice as likely to remain in the highest quartile at 3½-years for retinol (OR 2.21 (95% CI 1.48–3.28)) and carotene (OR 1.66 (95% CI 1.11–2.50)) than to change quartiles. Nutrient-rich core foods provided decreasing amounts of carotene and preformed retinol over time (both p < 0.001). Vegetables and milk contributed the highest proportion of carotene at both ages, but milk’s contribution decreased over time. Milk and liver were the largest sources of retinol. Nutrient-poor foods provided an increased proportion of energy (p < 0.001) with low proportions of both nutrients; however fat spreads made an important contribution. It is recommended that pre-school children should take vitamin supplements; only 19% at 18-months did this, falling to 11% at 3½-years. Care should be taken to choose nutrient-rich foods and avoid energy-dense, nutrient-poor foods when feeding pre-school children. Nutrients 2013-05-15 5 5 Article 10.3390/nu5051609 1609 1621 2072-6643 2013-05-15 doi: 10.3390/nu5051609 Victoria Cribb Kate Northstone David Hopkins Pauline Emmett http://www.mdpi.com/2072-6643/5/5/1595 It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia) may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life after bariatric surgery. The treatment of perioperative anaemia and nutrient deficiencies has been shown to improve patients’ outcomes and quality of life. All patients should undergo an appropriate nutritional evaluation, including selective micronutrient measurements (e.g., iron), before any bariatric surgical procedure. In comparison with purely restrictive procedures, more extensive perioperative nutritional evaluations are required for malabsorptive procedures due to their nutritional consequences. The aim of this study was to review the current knowledge of nutritional deficits in obese patients and those that commonly appear after bariatric surgery, specifically iron deficiencies and their consequences. As a result, some recommendations for screening and supplementation are presented. Nutrients 2013-05-15 5 5 Review 10.3390/nu5051595 1595 1608 2072-6643 2013-05-15 doi: 10.3390/nu5051595 Ignacio Jáuregui-Lobera http://www.mdpi.com/2072-6643/5/5/1585 A gluten-free diet (GFD) is the treatment for celiac disease (CD), but due to its complexity, dietitian referral is uniformly recommended. We surveyed patients with CD to determine if dietitian use is associated with quality of life, symptom severity, or GFD adherence. The survey utilized three validated CD-specific instruments: the CD quality of life (CD-QOL), CD symptom index (CSI) and CD adherence test (CDAT). Four hundred and thirteen patients with biopsy-proven CD were eligible for inclusion. The majority (77%) were female and mean BMI was 24.1. Over three-quarters of patients (326, 79%) had seen a dietitian, however, 161 (39%) had seen a dietitian only once. Age, sex, and education level were not associated with dietitian use; nor was BMI (24.6 vs. 24.0, p = 0.45). On multivariate analysis, adjusting for age gender, education, duration of disease, and body mass index, dietitian use was not associated with CD-QOL, CSI, or CDAT scores. Our survey did not show an association between dietitian use and symptom severity, adherence, or quality of life. Delay in diagnosis was associated with poorer outcomes. This is a preliminary study with several limitations, and further prospective analysis is needed to evaluate the benefits and cost-effectiveness of dietitian-referral in the care of celiac disease patients. Nutrients 2013-05-15 5 5 Article 10.3390/nu5051585 1585 1594 2072-6643 2013-05-15 doi: 10.3390/nu5051585 SriHari Mahadev Suzanne Simpson Benjamin Lebwohl Suzanne Lewis Christina Tennyson Peter Green http://www.mdpi.com/2072-6643/5/5/1573 Throughout history, chocolate has been used to treat a wide variety of ailments, and in recent years, multiple studies have found that chocolate can have positive health effects, providing evidence to a centuries-long established use; this acknowledgement, however, did not have a straight course, having been involved in religious, medical and cultural controversies. Christian Europe, in fact, feared the exhilarating effects of new drinks, such as chocolate, coffee and tea. Therefore, these beverages would have been banished, had not doctors and scientists explained that they were good for the body. The scientific debate, which reached its peak in Florence in the 18th century, regarded the therapeutic effectiveness of the various chocolate components: it was necessary to know their properties first, in order to prepare the best cacao concoction for every patient. When Dietetics separated from Medicine, however, chocolate acquired the role of vehicle for easing the administration of bitter medicines, being associated to different health problems. The recent rediscovery of the beneficial use of cacao and chocolate focuses upon its value as supplemental nutrition. Building a bridge to the past may be helpful to detect the areas where the potential health benefits of chocolate are likely to be further explored. Nutrients 2013-05-14 5 5 Introduction 10.3390/nu5051573 1573 1584 2072-6643 2013-05-14 doi: 10.3390/nu5051573 Donatella Lippi http://www.mdpi.com/2072-6643/5/5/1561 Background: Low levels of circulating vitamin D are more likely to be found in those with darker skin pigmentation, who live in areas of high latitude, and who wear more clothing. We examined the prevalence of vitamin D deficiency and inadequacy in newcomer immigrant and refugee children. Methods: We evaluated circulating vitamin D status of immigrant children at the national level. Subsequently, we investigated vitamin D intake, circulating vitamin D status, and total body bone mineral content (TBBMC) in newcomer children living in Saskatchewan. Results: In the sample of newcomer children in Saskatchewan, the prevalence of inadequacy in calcium and vitamin D intakes was 76% and 89.4%, respectively. Vitamin D intake from food/supplement was significantly higher in immigrants compared to refugees, which accords with the significant difference in serum status. Circulating vitamin D status indicated that 29% of participants were deficient and another 44% had inadequate levels of serum 25(OH)D for bone health. Dietary vitamin D intake, sex, region of origin, and length of stay in Canada were significant predictors of serum vitamin D status. Results for TBBMC revealed that 38.6% were found to have low TBBMC compared to estimated values for age, sex, and ethnicity. In the regression model, after controlling for possible confounders, children who were taller and had greater circulating vitamin D also had greater TBBMC. Nationally, immigrant children, particularly girls, have significantly lower plasma 25(OH)D than non-immigrant children. Interpretation: Newcomer immigrant and refugee children are at a high risk of vitamin D deficiency and inadequacy, which may have serious negative consequences for their health. Nutrients 2013-05-14 5 5 Article 10.3390/nu5051561 1561 1572 2072-6643 2013-05-14 doi: 10.3390/nu5051561 Hassanali Vatanparast Christine Nisbet Brian Gushulak http://www.mdpi.com/2072-6643/5/5/1544 Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease. Nutrients 2013-05-10 5 5 Review 10.3390/nu5051544 1544 1560 2072-6643 2013-05-10 doi: 10.3390/nu5051544 Melania Gaggini Mariangela Morelli Emma Buzzigoli Ralph DeFronzo Elisabetta Bugianesi Amalia Gastaldelli http://www.mdpi.com/2072-6643/5/5/1531 To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF), 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations. Nutrients 2013-05-08 5 5 Article 10.3390/nu5051531 1531 1543 2072-6643 2013-05-08 doi: 10.3390/nu5051531 Bruno Zappacosta Pierpaolo Mastroiacovo Silvia Persichilli George Pounis Stefania Ruggeri Angelo Minucci Emilia Carnovale Generoso Andria Roberta Ricci Iris Scala Orazio Genovese Aida Turrini Lorenza Mistura Bruno Giardina Licia Iacoviello http://www.mdpi.com/2072-6643/5/5/1511 Dietary patterns are sensitive to differences across socio-economic strata or cultural habits and may impact programing of diseases in later life. The purpose of this study was to identify distinct dietary patterns during pregnancy in the Mid-South using factor analysis. Furthermore, we aimed to analyze the differences in the food groups and in macro- and micronutrients among the different food patterns. The study was a cross-sectional analysis of 1155 pregnant women (mean age 26.5 ± 5.4 years; 62% African American, 35% Caucasian, 3% Other; and pre-pregnancy BMI 27.6 ± 7.5 kg/m2). Using food frequency questionnaire data collected from participants in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study between 16 and 28 weeks of gestation, dietary patterns were identified using factor analysis. Three major dietary patterns, namely, Healthy, Processed, and US Southern were identified among pregnant women from the Mid-South. Further analysis of the three main patterns revealed four mixed dietary patterns, i.e., Healthy-Processed, Healthy-US Southern, Processed-US Southern, and overall Mixed. These dietary patterns were different (p < 0.001) from each other in almost all the food items, macro- and micro nutrients and aligned across socioeconomic and racial groups. Our study describes unique dietary patterns in the Mid-South, consumed by a cohort of women enrolled in a prospective study examining the association of maternal nutritional factors during pregnancy that are known to affect brain and cognitive development by age 3. Nutrients 2013-05-03 5 5 Article 10.3390/nu5051511 1511 1530 2072-6643 2013-05-03 doi: 10.3390/nu5051511 Eszter Völgyi Kecia Carroll Marion Hare Karen Ringwald-Smith Chandrika Piyathilake Wonsuk Yoo Frances Tylavsky http://www.mdpi.com/2072-6643/5/5/1500 This study investigated the fermentation and microbiota profiles of three fibers, wheat dextrin (WD), partially hydrolyzed guar gum (PHGG), and inulin, since little is known about the effects of WD and PHGG on gut microbiota. A treatment of salivary amylase, pepsin, and pancreatin was used to better physiologic digestion. Fibers (0.5 g) were fermented in triplicate including a control group without fiber for 0, 4, 8, 12, and 24 h. Analysis of pH, gas volume, hydrogen and methane gases, and short chain fatty acid (SCFA) concentrations were completed at each time point. Quantitative polymerase chain reaction (qPCR) was used to measure Bifidobacteria and Lactobacillus CFUs at 24 h. WD produced the least gas during fermentation at 8, 12, and 24 h (P < 0.0001), while inulin produced the most by 8 h (P < 0.0001). Each fiber reached its lowest pH value at different time points with inulin at 8 h (mean ± SE) (5.94 ± 0.03), PHGG at 12 h (5.98 ± 0.01), and WD at 24 h (6.17 ± 0.03). All fibers had higher total SCFA concentrations compared to the negative control (P < 0.05) at 24 h. At 24 h, inulin produced significantly (P = 0.0016) more butyrate than WD with PHGG being similar to both. An exploratory microbial analysis (log10 CFU/µL) showed WD had CFU for Bifidobacteria (6.12) and Lactobacillus (7.15) compared with the control (4.92 and 6.35, respectively). Rate of gas production is influenced by fiber source and may affect tolerance in vivo. Exploratory microbiota data hint at high levels of Bifidobacteria for WD, but require more robust investigation to corroborate these findings. Nutrients 2013-05-03 5 5 Article 10.3390/nu5051500 1500 1510 2072-6643 2013-05-03 doi: 10.3390/nu5051500 Jackie Noack Derek Timm Ashok Hospattankar Joanne Slavin http://www.mdpi.com/2072-6643/5/5/1488 Cancer patients receiving chemotherapy often develop mucositis as a direct result of their treatment. Recently, the intestinal microbiota has attracted significant attention in the investigation of the pathobiology of mucositis, with a number of studies investigating the effects of chemotherapeutic agents on the microbiota. With significant effects on the intestinal microbiota occurring following the administration of chemotherapy, there is now interest surrounding the downstream pathological effects that may be associated with the altered intestinal ecology. This review seeks to identify links between signalling pathways previously demonstrated to have a role in the development of mucositis, and the altered intestinal microbiota. Nutrients 2013-04-29 5 5 Review 10.3390/nu5051488 1488 1499 2072-6643 2013-04-29 doi: 10.3390/nu5051488 Andrea Stringer http://www.mdpi.com/2072-6643/5/5/1471 Numerous studies reveal the cardiovascular benefits of consuming dietary fiber and, especially, cereal fiber. Cereal fiber is associated with cardiovascular risk reduction through multiple mechanisms and consuming a variety of cereal fiber sources offers health benefits specific to the source. Certain cereal fibers have been studied more extensively than others and provide greater support for their incorporation into a healthful diet. β-glucan from oats or barley, or a combination of whole oats and barley, and soluble fiber from psyllium reduces the risk of coronary heart disease; inulin-type fructans added to foods and beverages may modestly decrease serum triacylglycerols; arabinoxylan and resistant starch may improve glycemic control. Individuals with low cereal fiber intake should increase their intake of whole grains in order to receive the benefits of whole grains in addition to fiber. For those adjusting to the texture and palatability of whole grains, turning to added-fiber products rich in β-glucan and psyllium may allow them to reach their fiber goals without increasing caloric intake. Nutrients 2013-04-29 5 5 Review 10.3390/nu5051471 1471 1487 2072-6643 2013-04-29 doi: 10.3390/nu5051471 Adam Bernstein Brigid Titgemeier Kristin Kirkpatrick Mladen Golubic Michael Roizen http://www.mdpi.com/2072-6643/5/4/1456 End stage renal disease patients undergoing long-term dialysis are at risk for abnormal concentrations of certain essential and non-essential trace metals and high oxidative stress. We evaluated the effects of zinc (Zn) supplementation on plasma aluminum (Al) and selenium (Se) concentrations and oxidative stress in chronic dialysis patients. Zn-deficient patients receiving continuous ambulatory peritoneal dialysis or hemodialysis were divided into two groups according to plasma Al concentrations (HA group, Al > 50 μg/L; and MA group, Al > 30 to ≤ 50 μg/L). All patients received daily oral Zn supplements for two months. Age- and gender-matched healthy individuals did not receive Zn supplement. Clinical variables were assessed before, at one month, and after the supplementation period. Compared with healthy subjects, patients had significantly lower baseline plasma Se concentrations and higher oxidative stress status. After two-month Zn treatment, these patients had higher plasma Zn and Se concentrations, reduced plasma Al concentrations and oxidative stress. Furthermore, increased plasma Zn concentrations were related to the concentrations of Al, Se, oxidative product malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase activities. In conclusion, Zn supplementation ameliorates abnormally high plasma Al concentrations and oxidative stress and improves Se status in long-term dialysis patients. Nutrients 2013-04-22 5 4 Article 10.3390/nu5041456 1456 1470 2072-6643 2013-04-22 doi: 10.3390/nu5041456 Chih-Hung Guo Pei-Chung Chen Guoo-Shyng Hsu Chia-Liang Wang http://www.mdpi.com/2072-6643/5/4/1436 This study investigated whether increasing insoluble (predominantly wheat bran) fibre over 14 days improves subjective digestive feelings, general wellbeing and bowel function. A single centre, multi-site, open, within subjects design with a 14 day non-intervention (baseline) monitoring period followed by a 14 day fibre consumption (intervention) period was performed. 153 low fibre consumers (<15 g/day AOAC 985.29) completed a daily symptom diary for 14 days after which they consumed one bowl of ready-to-eat breakfast cereal containing at least 5.4 g fibre (3.5 g from wheat bran) for 14 days and completed a daily symptom diary. Significant improvements were demonstrated in subjective perception of bowel function (e.g., ease of defecation) and digestive feelings (bloating, constipation, feeling sluggish and digestive discomfort). Significant improvements were also found in subjective perception of general wellbeing (feeling less fat, more mentally alert, slim, happy and energetic whilst experiencing less stress, mental and physical tiredness, difficulty concentrating and fewer headaches). In general, improvements in study outcomes increased with increasing cereal/fibre consumption. However, consuming an additional minimum 5.4 g of fibre (3.5 g wheat bran) per day was shown to deliver measurable and significant benefits for digestive health, comfort and wellbeing. Encouraging consumption of relatively small amounts of wheat bran could also provide an effective method of increasing overall fibre consumption. Nutrients 2013-04-22 5 4 Article 10.3390/nu5041436 1436 1455 2072-6643 2013-04-22 doi: 10.3390/nu5041436 Clare Lawton Jenny Walton Alexa Hoyland Elaine Howarth Peter Allan David Chesters Louise Dye http://www.mdpi.com/2072-6643/5/4/1417 The health benefits of dietary fiber have long been appreciated. Higher intakes of dietary fiber are linked to less cardiovascular disease and fiber plays a role in gut health, with many effective laxatives actually isolated fiber sources. Higher intakes of fiber are linked to lower body weights. Only polysaccharides were included in dietary fiber originally, but more recent definitions have included oligosaccharides as dietary fiber, not based on their chemical measurement as dietary fiber by the accepted total dietary fiber (TDF) method, but on their physiological effects. Inulin, fructo-oligosaccharides, and other oligosaccharides are included as fiber in food labels in the US. Additionally, oligosaccharides are the best known “prebiotics”, “a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health.” To date, all known and suspected prebiotics are carbohydrate compounds, primarily oligosaccharides, known to resist digestion in the human small intestine and reach the colon where they are fermented by the gut microflora. Studies have provided evidence that inulin and oligofructose (OF), lactulose, and resistant starch (RS) meet all aspects of the definition, including the stimulation of Bifidobacterium, a beneficial bacterial genus. Other isolated carbohydrates and carbohydrate-containing foods, including galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), polydextrose, wheat dextrin, acacia gum, psyllium, banana, whole grain wheat, and whole grain corn also have prebiotic effects. Nutrients 2013-04-22 5 4 Review 10.3390/nu5041417 1417 1435 2072-6643 2013-04-22 doi: 10.3390/nu5041417 Joanne Slavin http://www.mdpi.com/2072-6643/5/4/1384 Several reviews and meta-analyses have examined the effects of iodine on mental development. None focused on young children, so they were incomplete in summarizing the effects on this important age group. The current systematic review therefore examined the relationship between iodine and mental development of children 5 years old and under. A systematic review of articles using Medline (1980–November 2011) was carried out. We organized studies according to four designs: (1) randomized controlled trial with iodine supplementation of mothers; (2) non-randomized trial with iodine supplementation of mothers and/or infants; (3) prospective cohort study stratified by pregnant women’s iodine status; (4) prospective cohort study stratified by newborn iodine status. Average effect sizes for these four designs were 0.68 (2 RCT studies), 0.46 (8 non-RCT studies), 0.52 (9 cohort stratified by mothers’ iodine status), and 0.54 (4 cohort stratified by infants’ iodine status). This translates into 6.9 to 10.2 IQ points lower in iodine deficient children compared with iodine replete children. Thus, regardless of study design, iodine deficiency had a substantial impact on mental development. Methodological concerns included weak study designs, the omission of important confounders, small sample sizes, the lack of cluster analyses, and the lack of separate analyses of verbal and non-verbal subtests. Quantifying more precisely the contribution of iodine deficiency to delayed mental development in young children requires more well-designed randomized controlled trials, including ones on the role of iodized salt. Nutrients 2013-04-22 5 4 Review 10.3390/nu5041384 1384 1416 2072-6643 2013-04-22 doi: 10.3390/nu5041384 Karim Bougma Frances Aboud Kimberly Harding Grace Marquis http://www.mdpi.com/2072-6643/5/4/1366 Low HDL-cholesterol (HDL-C), using as cut-offs 1.03 mmol/L in men and 1.29 mmol/L in women, was observed in more than 25% apparently healthy adults (n = 541) in a cross-sectional study on nutrition transition and cardiometabolic risk factors (CMRF) in Benin, West Africa. Both overweight/obesity (35.3%) and underweight (11.3%) were present, displaying the double burden of malnutrition. We examined in more depth the association of low HDL-C with nutrition and with other CMRF. Metabolic syndrome components were assessed, plus the ratio of total cholesterol (TC)/HDL-C and serum homocysteine. Insulin resistance was based on Homeostasis Model Assessment. We also measured BMI and body composition by bio-impedance. Dietary quality was appraised with two non-consecutive 24 h recalls. Low HDL-C was associated with much higher TC/HDL-C and more abdominal obesity in men and women and with more insulin resistance in women. The rate of low HDL-C was highest (41.9%) among the overweight/obese subjects (BMI ≥ 25), but it also reached 31.1% among the underweight (BMI < 18.5), compared with 17.3% among normal-weight subjects (p < 0.001). Lower dietary micronutrient adequacy, in particular, in vitamins A, B3, B12, zinc and calcium, was associated with low HDL-C when controlling for several confounders. This suggests that at-risk lipoprotein cholesterol may be associated with either underweight or overweight/obesity and with poor micronutrient intake. Nutrients 2013-04-19 5 4 Article 10.3390/nu5041366 1366 1383 2072-6643 2013-04-19 doi: 10.3390/nu5041366 Hélène Delisle Gervais Ntandou Roger Sodjinou Charles Couillard Jean-Pierre Després http://www.mdpi.com/2072-6643/5/4/1349 Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases. Nutrients 2013-04-19 5 4 Review 10.3390/nu5041349 1349 1365 2072-6643 2013-04-19 doi: 10.3390/nu5041349 Caroline Rocourt Wen-Hsing Cheng http://www.mdpi.com/2072-6643/5/4/1336 Aim: Uremic hyperparathyroidism (UHPT) has been shown to contribute to the development and progression of chronic kidney disease—mineral bone disorder. UHPT is frequently observed in chronic dialysis patients, and patients with UHPT are associated with increased risk of all-cause and cardiovascular mortality. Cinacalcet is a novel agent that increases sensitivity to the calcium-sensing receptor and is approved for control of UHPT. Nevertheless, cinacalcet is costly and information regarding efficacy of low-dose cinacalcet on UHPT is limited. Methods: We conducted a retrospective study to evaluate treatment with either low-dose calcitriol combined with low-dose cinacalcet (25 mg) (d-Cinacalcet) or calcitriol alone (VitD) in dialysis patients with moderate to severe UHPT. A total of 81 dialysis patients were enrolled (40 subjects in d-Cinacalcet group and 41 subjects in VitD group). Demographic data including age, gender, duration on dialysis and biochemical data were reviewed and recorded. Results: At the end of the study, the intact parathyroid hormone (iPTH) levels of the d-Cinacalcet group declined significantly (from 1166.0 ± 469.3 pg/mL to 679.8 ± 421.6 pg/mL, p < 0.0001), while there was no significant change in the VitD group. Significant decrease of serum calcium (Ca: 9.9 ± 0.6 mg/dL vs. 9.6 ± 0.8 mg/dL, p = 0.002), phosphorus (P: 5.9 ± 1.3 mg/dL vs. 4.9 ± 0.9 mg/dL, p < 0.0001) and calcium phosphate product (Ca × P: 58.7 ± 15.0 mg2/dL2 vs. 46.9 ± 8.9 mg2/dL2, p < 0.0001) were observed in the d-Cinacalcet group. In addition, the subjects in the d-Cinacalcet group had a greater proportion to achieve Kidney Disease Outcomes Quality Initiative (KDOQI)-recommended biochemical targets than the subjects in the VitD group (Ca: 48% vs. 24%; P: 78% vs. 32%; Ca × P: 85% vs. 37%; iPTH: 15% vs. 0%). Conclusions: We conclude that combination therapy of low-dose cinacalcet and calcitriol is more effective than calcitriol alone as a treatment for moderate and severe UHPT in chronic dialysis patients. Furthermore, this therapy is associated with improvement in hyperphosphatemia and hypercalcemia. Nutrients 2013-04-19 5 4 Article 10.3390/nu5041336 1336 1348 2072-6643 2013-04-19 doi: 10.3390/nu5041336 Yueh-Ting Lee Hwee-Yeong Ng Chien-Chun Kuo Te-Chuan Chen Chien-Shing Wu Terry Chiu Wen-Chin Lee Chien-Te Lee http://www.mdpi.com/2072-6643/5/4/1316 Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung and whole body caused mainly by tobacco smoking. Patients with advanced COPD are in a state of undernutrition, referred to as pulmonary cachexia; the exercise performance and quality of life (QOL) of these patients are deteriorated, the vital prognosis is unfavorable, and the medico-economic burden posed by poorly nourished COPD patients is high. The mainstays of COPD treatment are pharmacotherapy, mainly with bronchodilators, and non-pharmacotherapeutic approaches such as respiratory rehabilitation and nutrition counseling. Nutritional supplement therapy, consisting primarily of high calorie intake, has been demonstrated to be effective for maintaining and improving the muscle strength and exercise tolerance in poorly nourished COPD patients. The efficacy of intake of various nutrients, besides a high calorie intake, for amelioration of the disease state of COPD has also been reported. The roles of adipokines in the pathophysiology of COPD have begun to receive attention recently, and not only their regulatory effects on appetite and nutritional status, but also their influence on systemic inflammation have been increasingly clarified. We review the papers on COPD and nutrition and discuss the role of nutritional supplement therapy in the treatment of COPD. Nutrients 2013-04-18 5 4 Review 10.3390/nu5041316 1316 1335 2072-6643 2013-04-18 doi: 10.3390/nu5041316 Masayuki Itoh Takao Tsuji Kenji Nemoto Hiroyuki Nakamura Kazutetsu Aoshiba http://www.mdpi.com/2072-6643/5/4/1301 Increasing demand for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) containing fish oils is putting pressure on fish species and numbers. Fisheries provide fish for human consumption, supplement production and fish feeds and are currently supplying fish at a maximum historical rate, suggesting mass-scale fishing is no longer sustainable. However, the health properties of EPA and DHA long-chain (LC) omega-3 polyunsaturated fatty acids (PUFA) demonstrate the necessity for these oils in our diets. EPA and DHA from fish oils show favourable effects in inflammatory bowel disease, some cancers and cardiovascular complications. The high prevalence of these diseases worldwide indicates the requirement for alternative sources of LC-PUFA. Strategies have included plant-based fish diets, although this may compromise the health benefits associated with fish oils. Alternatively, stearidonic acid, the product of α-linolenic acid desaturation, may act as an EPA-enhancing fatty acid. Additionally, algae oils may be a promising omega-3 PUFA source for the future. Algae are beneficial for multiple industries, offering a source of biodiesel and livestock feeds. However, further research is required to develop efficient and sustainable LC-PUFA production from algae. This paper summarises the recent research for developing prospective substitutes for omega-3 PUFA and the current limitations that are faced. Nutrients 2013-04-18 5 4 Review 10.3390/nu5041301 1301 1315 2072-6643 2013-04-18 doi: 10.3390/nu5041301 Georgia Lenihan-Geels Karen Bishop Lynnette Ferguson http://www.mdpi.com/2072-6643/5/4/1287 Excess dietary fat consumption is recognized as a strong contributing factor in the development of overweight and obesity. Understanding why some individuals are better than others at regulating fat intake will become increasingly important and emerging associative evidence implicates attenuated fatty acid sensing in both the oral cavity and gastrointestinal (GI) tract in the development of obesity. Functional implications of impaired fatty acid chemoreception include diminished activation of the gustatory system, the cephalic response and satiety. This review will focus on knowledge from animal and human studies supporting the existence of oral fatty acid chemoreception including putative oral detection mechanisms, and how sensitivity to fatty acids is associated with fat consumption and fatty food preference. Nutrients 2013-04-17 5 4 Review 10.3390/nu5041287 1287 1300 2072-6643 2013-04-17 doi: 10.3390/nu5041287 Lisa Newman Rivkeh Haryono Russell Keast http://www.mdpi.com/2072-6643/5/4/1276 We hypothesize that improvements in the gut microbiota are capable of ameliorating gut permeability and, consequently, reducing systemic inflammation and the risk of frailty. This study aims to evaluate some effects of synbiotic supplementation on inflammatory markers and the body composition of the elderly at risk of frailty. In a double-blind study that lasted three months, 17 elderly individuals fulfilling one frailty criteria (grip strength) were randomly distributed into two groups: SYN (n = 9), daily intake of synbiotic (6 g Frutooligossacarides, 108 to 109 CFU Lactobacillus paracasei, 108 to 109 CFU Lactobacillus rhamnosus, 108 to 109 CFU Lactobacillus acidophilus and 108 to 109 CFU Bifidobacterium lactis), or placebo (maltodextrin; PLA; n = 8). Subjects were analyzed for anthropometric measurements, bioelectric impedance with vectorial analysis (BIVA), IL-6 and TNF-α. A comparison between groups did not show any difference for the variables investigated. In turn, individual analysis of electrical impedance (BIVA) demonstrated that the majority of SYN individuals maintained or improved their tissue hydration, when compared to the PLA group after supplementation. In conclusion, three months of synbiotic supplementation did not promote any significant changes in inflammatory cytokines or body composition, but demonstrated a trend towards a preservation of hydration status in apparently healthy elderly individuals. Nutrients 2013-04-17 5 4 Article 10.3390/nu5041276 1276 1286 2072-6643 2013-04-17 doi: 10.3390/nu5041276 João Neto Camila de Melo Sandra Ribeiro http://www.mdpi.com/2072-6643/5/4/1253 The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject had one leg randomly assigned as a control. The other leg performed an intense exercise protocol. Single-leg peak isometric force and blood 25(OH)D, aspartate and alanine aminotransferases, albumin, interferon (IFN)-γ, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH)D concentrations increased (p < 0.05) immediately, but within minutes, subsequently decreased (p < 0.05). Circulating albumin increases predicted (p < 0.005) serum 25(OH)D increases, while IFN-γ increases predicted (p < 0.001) serum 25(OH)D decreases. Muscular weakness persisted within the exercise leg (p < 0.05) and compared to the control leg (p < 0.05) after the exercise protocol. Serum 25(OH)D concentrations inversely predicted (p < 0.05) muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days (i.e., 48-h and 72-h) after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH)D prior to exercise. Based on these data, we conclude that pre-exercise serum 25(OH)D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise. Nutrients 2013-04-17 5 4 Article 10.3390/nu5041253 1253 1275 2072-6643 2013-04-17 doi: 10.3390/nu5041253 Tyler Barker Vanessa Henriksen Thomas Martins Harry Hill Carl Kjeldsberg Erik Schneider Brian Dixon Lindell Weaver http://www.mdpi.com/2072-6643/5/4/1241 Lipid and protein oxidation decreases the shelf-life of foods and may result in formation of end-products potentially detrimental for health. Consumer pressure to decrease the use of synthetic phenolic antioxidants has encouraged identification of alternative compounds or extracts from natural sources. We have assessed whether inclusion of dried vegetable powders improves the oxidative stability of turkey meat patties. Such powders are not only potentially-rich sources of phenolic antioxidants, but also may impart additional health benefits, as inadequate vegetable consumption is a risk factor for heart disease and several cancers. In an accelerated oxidation system, six of eleven vegetable powders significantly (p < 0.05) improved oxidative stability of patties by 20%–30% (spinach < yellow pea < onion < red pepper < green pea < tomato). Improved lipid oxidative stability was strongly correlated with the decreased formation of protein carbonyls (r = 0.747, p < 0.01). However, improved lipid stability could not be ascribed to phenolic acids nor recognized antioxidants, such as α- and γ-tocopherol, despite their significant (p < 0.01) contribution to the total antioxidant capacity of the patties. Use of chemically complex vegetable powders offers an alternative to individual antioxidants for increasing shelf-life of animal-based food products and may also provide additional health benefits associated with increased vegetable intake. Nutrients 2013-04-17 5 4 Article 10.3390/nu5041241 1241 1252 2072-6643 2013-04-17 doi: 10.3390/nu5041241 Garry Duthie Fiona Campbell Charles Bestwick Sylvia Stephen Wendy Russell http://www.mdpi.com/2072-6643/5/4/1218 Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia. Nutrients 2013-04-12 5 4 Review 10.3390/nu5041218 1218 1240 2072-6643 2013-04-12 doi: 10.3390/nu5041218 Boudewijn Klop Jan Elte Manuel Cabezas http://www.mdpi.com/2072-6643/5/4/1200 Aims: Dietary antioxidants, including vitamin C, may be in part responsible for the cancer-preventive effects of fruits and vegetables. Human intervention trials with clinical endpoints have failed to confirm their protective effects, and mechanistic studies have given inconsistent results. Our aim was to investigate antioxidant/ pro-oxidant effects of vitamin C at the cellular level. Experimental approach: We have used the comet assay to investigate effects of vitamin C on DNA damage, antioxidant status, and DNA repair, in HeLa (human tumor) cells, and HPLC to measure uptake of vitamin C into cells. Results: Even at concentrations in the medium as high as 200 μM, vitamin C did not increase the background level of strand breaks or of oxidized purines in nuclear DNA. Vitamin C is taken up by HeLa cells and accumulates to mM levels. Preincubation of cells with vitamin C did not render them resistant to strand breakage induced by H2O2 or to purine oxidation by photosensitizer plus light. Vitamin C had no effect on the rate of repair of strand breaks or oxidized bases by HeLa cells. However, vitamin C at a concentration of less than 1 μM, or extract from cells preincubated for 6 h with vitamin C, was able to induce damage (strand breaks) in lysed, histone-depleted nuclei (nucleoids). Conclusion: In these cultured human cells, vitamin C displays neither antioxidant nor pro-oxidant properties; nor does it affect DNA strand break or base excision repair. Nutrients 2013-04-09 5 4 Article 10.3390/nu5041200 1200 1217 2072-6643 2013-04-09 doi: 10.3390/nu5041200 Amaya Azqueta Solange Costa Yolanda Lorenzo Nasser Bastani Andrew Collins http://www.mdpi.com/2072-6643/5/4/1186 Limited work is available on the benefits of nutritional support enriched with arginine and n-3 fatty acids in surgical patients with head and neck cancer, particularly if well-nourished. We conducted a pilot study in these patients to examine effects on inflammatory markers and clinical outcome. Patients scheduled for radical resection of the oral cavity were randomised to 5 day preoperative and 5 day postoperative Impact® (IMN, n = 4), or no preoperative supplementary nutrition and Isosource® postoperatively (STD, n = 4). Plasma fatty acids, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured at baseline, day of surgery and on postoperative days (POD) 2, 4 and 10. Postoperative complications were recorded. The (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid ratio was significantly higher in IMN patients on POD 2, 4 and 10 (P < 0.01). While not statistically significant, CRP, TNF-α, and IL-6 concentrations were higher in the STD group on POD2 while IL-10 was lower. Median length of stay was 10 (range 10–43) days in the IMN group and 21.5 (7–24) days in the STD group. Five complications were seen in the STD group and two in the IMN group. The results support the need for a larger trial focusing on clinical outcome. Nutrients 2013-04-09 5 4 Article 10.3390/nu5041186 1186 1199 2072-6643 2013-04-09 doi: 10.3390/nu5041186 Amy Turnock Philip Calder Annette West Mark Izzard Randall Morton Lindsay Plank http://www.mdpi.com/2072-6643/5/4/1169 The eye is a major sensory organ that requires special care for a healthy and productive lifestyle. Numerous studies have identified lutein and zeaxanthin to be essential components for eye health. Lutein and zeaxanthin are carotenoid pigments that impart yellow or orange color to various common foods such as cantaloupe, pasta, corn, carrots, orange/yellow peppers, fish, salmon and eggs. Their role in human health, in particular the health of the eye, is well established from epidemiological, clinical and interventional studies. They constitute the main pigments found in the yellow spot of the human retina which protect the macula from damage by blue light, improve visual acuity and scavenge harmful reactive oxygen species. They have also been linked with reduced risk of age-related macular degeneration (AMD) and cataracts. Research over the past decade has focused on the development of carotenoid-rich foods to boost their intake especially in the elderly population. The aim of this article is to review recent scientific evidences supporting the benefits of lutein and zexanthin in preventing the onset of two major age-related eye diseases with diets rich in these carotenoids. The review also lists major dietary sources of lutein and zeaxanthin and refers to newly developed foods, daily intake, bioavailability and physiological effects in relation to eye health. Examples of the newly developed high-lutein functional foods are also underlined. Nutrients 2013-04-09 5 4 Review 10.3390/nu5041169 1169 1185 2072-6643 2013-04-09 doi: 10.3390/nu5041169 El-Sayed Abdel-Aal Humayoun Akhtar Khalid Zaheer Rashida Ali http://www.mdpi.com/2072-6643/5/4/1149 Selenium (Se) is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent. Nutrients 2013-04-08 5 4 Review 10.3390/nu5041149 1149 1168 2072-6643 2013-04-08 doi: 10.3390/nu5041149 Yu-Chi Chen K. Prabhu Andrea Mastro http://www.mdpi.com/2072-6643/5/4/1122 The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. Nutrients 2013-04-03 5 4 Review 10.3390/nu5041122 1122 1148 2072-6643 2013-04-03 doi: 10.3390/nu5041122 Holly Nicastro Barbara Dunn http://www.mdpi.com/2072-6643/5/4/1110 Dietary supplement use may modify the risk of periodontal disease but effects on wound healing after periodontal procedures are less clear. This study characterized dietary supplement use by male and female patients (n = 376) attending a periodontal clinic—information that is essential for evidence-based intervention studies that may improve patient outcomes after periodontal procedures. Calcium, vitamin D, multivitamin and vitamin C were most commonly used. A greater (p ≤ 0.05) number of males took no supplements compared to females, and more (p ≤ 0.05) females than males took ≥ four supplements. Females took more (p ≤ 0.05) calcium, vitamin D, fish oil, green tea, magnesium, omega 3,6,9 and B vitamin complex. Younger patients (31–50 years) had the highest (p ≤ 0.05) frequency of no supplement use compared to older age groups. Patients over age 50 had a higher (p ≤ 0.05) frequency of using ≥ four supplements including calcium and vitamin D. Supplement use was lower (p ≤ 0.05) in smokers, particularly for calcium, fish oil, green tea and vitamin D. In conclusion, females, older individuals and non-smokers have higher supplement use. Future dietary intervention studies can focus on supplements with known biological activities—anti-inflammatory, antioxidant or osteogenic activity—that may enhance wound healing after reconstructive periodontal procedures. Nutrients 2013-04-02 5 4 Article 10.3390/nu5041110 1110 1121 2072-6643 2013-04-02 doi: 10.3390/nu5041110 Bryan Johnston Peter Fritz Wendy Ward http://www.mdpi.com/2072-6643/5/4/1098 Pregnant women do not currently meet the consensus recommendation for docosahexaenoic acid (DHA) (≥200 mg/day). Pregnant women in Australia are not receiving information on the importance of DHA during pregnancy. DHA pregnancy education materials were developed using current scientific literature, and tested for readability and design aesthetics. The study aimed to evaluate their usefulness, the desire for pregnant women to receive these materials and whether a larger separate study (using a control group) is warranted to evaluate the influence the materials may have on increasing DHA consumption in pregnant women in Australia. Pregnant women (N = 118) were recruited at antenatal clinics at two NSW hospitals. Participants completed a 16-item questionnaire and DHA educational materials (pamphlet and shopping card) were provided. Participants were contacted via phone two weeks later and completed the second questionnaire (25-item, N = 74). Statistics were conducted in SPSS and qualitative data were analysed to identify common themes. Ninety three percent of women found the materials useful, with the main reason being it expanded their knowledge of DHA food sources. Only 34% of women had received prior information on DHA, yet 68% said they would like to receive information. Due to the small sample size and lack of a control group, this small study cannot provide a cause and effect relationship between the materials and nutrition related behaviours or knowledge, however the results indicate a potential positive influence towards increased fish consumption and awareness of DHA containing foods. This suggests a larger study, with a control group is warranted to identify the impact such materials could have on Australian pregnant women. Nutrients 2013-04-02 5 4 Article 10.3390/nu5041098 1098 1109 2072-6643 2013-04-02 doi: 10.3390/nu5041098 Rebecca Emmett Shann Akkersdyk Heather Yeatman Barbara Meyer http://www.mdpi.com/2072-6643/5/4/1081 Increasing fish consumption is recommended for intake of omega-3 (n-3) fatty acids and to confer benefits for the risk reduction of cardiovascular disease (CVD). Most Americans are not achieving intake levels that comply with current recommendations. It is the goal of this review to provide an overview of the issues affecting this shortfall of intake. Herein we describe the relationship between fish intake and CVD risk reduction as well as the other nutritional contributions of fish to the diet. Currently recommended intake levels are described and estimates of fish consumption at a food disappearance and individual level are reported. Risk and benefit factors influencing the choice to consume fish are outlined. The multiple factors influencing fish availability from global capture and aquaculture are described as are other pertinent issues of fish nutrition, production, sustainability, and consumption patterns. This review highlights some of the work that needs to be carried out to meet the demand for fish and to positively affect intake levels to meet fish intake recommendations for CVD risk reduction. Nutrients 2013-03-28 5 4 Review 10.3390/nu5041081 1081 1097 2072-6643 2013-03-28 doi: 10.3390/nu5041081 Susan Raatz Jeffrey Silverstein Lisa Jahns Matthew Picklo http://www.mdpi.com/2072-6643/5/4/1071 Despite a considerable amount of data available on the relationship between dietary glycemic index (GI) or load (GL) and cardiovascular disease (CVD) risk factors, in aggregate, the area remains unsettled. The aim of the present review was to summarize the effect of diets differing in GI/GL on CVD risk factors, by examining randomized controlled-feeding trials that provided all food and beverages to adult participants. The studies included a low and high GI/GL diet phase for a minimum of four weeks duration, and reported at least one outcome related to CVD risk; glucose homeostasis, lipid profile or inflammatory status. Ten publications representing five trials were identified. The low GI/GL compared to the high GI/GL diet unexpectedly resulted in significantly higher fasting glucose concentrations in two of the trials, and a lower area under the curve for glucose and insulin in one of the two studies during an oral glucose tolerance test. Response of plasma total, low density lipoprotein and high density lipoprotein cholesterol concentrations was conflicting in two of the studies for which data were available. There was either weak or no effect on inflammatory markers. The results of the five randomized controlled trials satisfying the inclusion criteria suggest inconsistent effects of the GI/GL value of the diet on CVD risk factors. Nutrients 2013-03-28 5 4 Review 10.3390/nu5041071 1071 1080 2072-6643 2013-03-28 doi: 10.3390/nu5041071 Aleksandra Kristo Nirupa Matthan Alice Lichtenstein http://www.mdpi.com/2072-6643/5/4/1058 Parenteral nutrition (PN) has become an integral part of clinical management of very low birth weight premature neonates. Traditionally different components of PN are prescribed individually considering requirements of an individual neonate (IPN). More recently, standardised PN formulations (SPN) for preterm neonates have been assessed and may have advantages including better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bag that provides total nutrient admixture for neonates may have additional advantage of decreased risk of contamination and ease of administration. Nutrients 2013-03-28 5 4 Review 10.3390/nu5041058 1058 1070 2072-6643 2013-03-28 doi: 10.3390/nu5041058 Karen Simmer Abhijeet Rakshasbhuvankar Girish Deshpande http://www.mdpi.com/2072-6643/5/4/1024 Use of dietary supplements in the U.S. has increased steadily over the last 25 years. While misformulation is uncommon, the consequences can be serious. A March 2008 voluntary market recall removed supplement products responsible for the most serious selenium toxicity outbreak that has occurred in the U.S. We quantified selenium concentrations in the misformulated supplement products, measured the temporal response in the nail biologic monitor, and associated exposure to self-reported selenosis symptoms. Subjects recruited through state health departments and referrals provided samples of the misformulated supplement products, exposure information, monthly toenail and or fingernail clippings or onycholysitic nail fragments, and listed their newly onset adverse health effects attributed to selenium toxicity. Ninety-seven subjects enrolled and submitted at least one test sample. Peak selenium concentrations (up to 18.3 and 44.1 μg/g for toenails and fingernails, respectively) were measured. Multiple samples (52 total) of all six recalled supplement lots were analyzed ranging from 22,300 to 32,200 μg selenium per daily dose. Average consumption was 30.9 ± 13.9 doses; 73 subjects provided follow-up data on selenosis symptoms at 2.50 ± 0.14 years. Nail samples accurately reflect exposure in this selenium toxicity outbreak, which resulted in long-term/permanent adverse health effects. Nutrients 2013-03-28 5 4 Article 10.3390/nu5041024 1024 1057 2072-6643 2013-03-28 doi: 10.3390/nu5041024 John Morris Stacy Crane http://www.mdpi.com/2072-6643/5/3/1002 The survival rate of dialysis patients, as determined by risk factors such as hypertension, nutritional status, and chronic inflammation, is lower than that of the general population. In addition, disorders of bone mineral metabolism are independently related to mortality and morbidity associated with cardiovascular disease and fracture in dialysis patients. Hyperphosphatemia is an important risk factor of, not only secondary hyperparathyroidism, but also cardiovascular disease. On the other hand, the risk of death reportedly increases with an increase in adjusted serum calcium level, while calcium levels below the recommended target are not associated with a worsened outcome. Thus, the significance of target levels of serum calcium in dialysis patients is debatable. The consensus on determining optimal parathyroid function in dialysis patients, however, is yet to be established. Therefore, the contribution of phosphorus and calcium levels to prognosis is perhaps more significant. Elevated fibroblast growth factor 23 levels have also been shown to be associated with cardiovascular events and death. In this review, we examine the associations between mineral metabolic abnormalities including serum phosphorus, calcium, and parathyroid hormone and mortality in dialysis patients. Nutrients 2013-03-22 5 3 Review 10.3390/nu5031002 1002 1023 2072-6643 2013-03-22 doi: 10.3390/nu5031002 Masanori Abe Kazuyoshi Okada Masayoshi Soma http://www.mdpi.com/2072-6643/5/3/981 Hypertriglyceridemia (HTG) is commonly encountered in lipid and cardiology clinics. Severe HTG warrants treatment because of the associated increased risk of acute pancreatitis. However, the need to treat, and the correct treatment approach for patients with mild to moderate HTG are issues for ongoing evaluation. In the past, it was felt that triglyceride does not directly contribute to development of atherosclerotic plaques. However, this view is evolving, especially for triglyceride-related fractions and variables measured in the non-fasting state. Our understanding of the etiology, genetics and classification of HTG states is also evolving. Previously, HTG was considered to be a dominant disorder associated with variation within a single gene. The old nomenclature includes the term “familial” in the names of several hyperlipoproteinemia (HLP) phenotypes that included HTG as part of their profile, including combined hyperlipidemia (HLP type 2B), dysbetalipoproteinemia (HLP type 3), simple HTG (HLP type 4) and mixed hyperlipidemia (HLP type 5). This old thinking has given way to the idea that genetic susceptibility to HTG results from cumulative effects of multiple genetic variants acting in concert. HTG most is often a “polygenic” or “multigenic” trait. However, a few rare autosomal recessive forms of severe HTG have been defined. Treatment depends on the overall clinical context, including severity of HTG, concomitant presence of other lipid disturbances, and the patient's global risk of cardiovascular disease. Therapeutic strategies include dietary counselling, lifestyle management, control of secondary factors, use of omega-3 preparations and selective use of pharmaceutical agents. Nutrients 2013-03-22 5 3 Article 10.3390/nu5030981 981 1001 2072-6643 2013-03-22 doi: 10.3390/nu5030981 Amanda Brahm Robert Hegele http://www.mdpi.com/2072-6643/5/3/971 This study compared two methods of assaying the 25-hydroxylated metabolites of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). A fully automated electrochemiluminescence assay from Roche Diagnostics and an HPLC based method from Chromsystems were used to measure vitamin D levels in surplus sera from 96 individuals, where the majority has the D2 form of the vitamin. Deming regression, concordance rate, correlation and Altman Bland agreement were performed. Seventy two subjects (75%) had a D2 concentration >10 nmol/L while the remaining twenty four subjects had vitamin D2 concentration of less than 10 nmol/L by HPLC. Overall, the Roche Diagnostics method showed a negative bias of −2.59 ± 4.11 nmol/L on the e602 as compared to the HPLC with a concordance rate of 84%. The concordance rate was 91% in samples with D2 of less than 10 nmol/L and 82% in those with D2 concentration >10 nmol/L. The overall correlation had an r value of 0.77. The r value was higher in samples with D2 levels of less than 10 nmol/L, r = 0.96, as compared to those with D2 values of greater than 10 nmol/L, r = 0.74. The observed bias had little impact on clinical decision and therefore is clinically acceptable. Nutrients 2013-03-22 5 3 Article 10.3390/nu5030971 971 980 2072-6643 2013-03-22 doi: 10.3390/nu5030971 Laila Abdel-Wareth Afrozul Haq Andrew Turner Shoukat Khan Arwa Salem Faten Mustafa Nafiz Hussein Fasila Pallinalakam Louisa Grundy Gemma Patras Jaishen Rajah http://www.mdpi.com/2072-6643/5/3/957 Iron is an essential nutrient for almost every living organism because it is required in a number of biological processes that serve to maintain life. In humans, recycling of senescent erythrocytes provides most of the daily requirement of iron. In addition, we need to absorb another 1–2 mg Fe from the diet each day to compensate for losses due to epithelial sloughing, perspiration, and bleeding. Iron absorption in the intestine is mainly regulated on the enterocyte level by effectors in the diet and systemic regulators accessing the enterocyte through the basal lamina. Recently, a complex meshwork of interactions between several trace metals and regulatory proteins was revealed. This review focuses on advances in our understanding of Cu, Zn, and Ca in the regulation of iron absorption. Ascorbate as an important player is also considered. Nutrients 2013-03-20 5 3 Review 10.3390/nu5030957 957 970 2072-6643 2013-03-20 doi: 10.3390/nu5030957 Nathalie Scheers http://www.mdpi.com/2072-6643/5/3/949 Obesity is a significant health problem world-wide, particularly in developed nations. Vitamin D deficiency is pandemic, and has been implicated in a wide variety of disease states. This paper seeks to examine the consistently reported relationship between obesity and low vitamin D concentrations, with reference to the possible underlying mechanisms. The possibility that vitamin D may assist in preventing or treating obesity is also examined, and recommendations for future research are made. There is a clear need for adequately-powered, prospective interventions which include baseline measurement of 25D concentrations and involve adequate doses of supplemental vitamin D. Until such studies have been reported, the role of vitamin D supplementation in obesity prevention remains uncertain. Nutrients 2013-03-20 5 3 Review 10.3390/nu5030949 949 956 2072-6643 2013-03-20 doi: 10.3390/nu5030949 Simon Vanlint http://www.mdpi.com/2072-6643/5/3/928 Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. Nutrients 2013-03-18 5 3 Review 10.3390/nu5030928 928 948 2072-6643 2013-03-18 doi: 10.3390/nu5030928 Dragana Nikolic Niki Katsiki Giuseppe Montalto Esma Isenovic Dimitri Mikhailidis Manfredi Rizzo http://www.mdpi.com/2072-6643/5/3/915 Objective: In Australia, vitamin D supply in food is limited, and sun exposure is the main source of vitamin D. However skin cancer risk is high, and the need to gain some sun exposure for adequate vitamin D is challenging public health messages to use protection in the sun. The complex vitamin D public health message may be confusing the public and, in particular, those at highest risk for vitamin D deficiency. This study explored vitamin D and sun exposure attitudes, knowledge and practices of some groups considered at risk of vitamin D deficiency and those delivering healthy sun exposure messages to children. Method: 52 adults participated in six focus groups. Results: Results corroborated with previous research showing low levels of vitamin D knowledge. Individual and environmental barriers to receiving adequate sun exposure were also identified. Conclusions and Implications: The message advocating balanced sun exposure to produce adequate vitamin D needs to be made clearer and be more effectively communicated. Findings provide insights to aid development of appropriate public health messages for safe sun exposure and vitamin D, especially for vulnerable groups. Nutrients 2013-03-15 5 3 Article 10.3390/nu5030915 915 927 2072-6643 2013-03-15 doi: 10.3390/nu5030915 Billie Bonevski Jamie Bryant Sylvie Lambert Irena Brozek Vanessa Rock http://www.mdpi.com/2072-6643/5/3/887 Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders. Nutrients 2013-03-15 5 3 Review 10.3390/nu5030887 887 914 2072-6643 2013-03-15 doi: 10.3390/nu5030887 Margaret Dauncey http://www.mdpi.com/2072-6643/5/3/877 The purpose of this 42-day study was to investigate the effects of methionine (Met) deficiency on immune function by determining the relative weight, morphological and ultrastructural changes of bursae of Fabricius, cell cycle, and apoptosis of bursa cells. One hundred and twenty one-day-old avian broilers were randomly divided into two groups and fed on a control diet (starter diet, Met 0.50%; grower diet, Met 0.40%) and Met-deficient diet (starter diet, Met 0.26%; grower diet, Met 0.28%) for six weeks. The relative weight of bursae was decreased with Met deficiency when compared to that of the control group. Lesions were also observed in the Met-deficient group. Histopathologically, the numbers of lymphocytes in the follicles were decreased. Ultrastructurally, the mitochondria of lymphocytes were swollen in the Met-deficient group. As measured by flow cytometry, bursal cells in the G0G1 phase were significantly higher (P < 0.01), and bursal cells in the S, G2M phases and proliferating index were obviously lower (P < 0.01) with Met deficiency than in the control group. Moreover, the percentage of apoptotic cells in the bursae were significantly increased in Met-deficient birds (P < 0.01). It was concluded that Met deficiency restrained the development of the bursae of Fabricius and affected the humoral immunity of the chickens. Nutrients 2013-03-13 5 3 Article 10.3390/nu5030877 877 886 2072-6643 2013-03-13 doi: 10.3390/nu5030877 Bangyuan Wu Hengmin Cui Xi Peng Jing Fang Wei Cui Xiaodong Liu http://www.mdpi.com/2072-6643/5/3/852 Ingestion of protein is crucial for maintenance of a variety of body functions and within the scope of this review we will specifically focus on the regulation of skeletal muscle mass. A quantitative limitation exists as to how much muscle protein the body can synthesize in response to protein intake. Ingestion of excess protein exerts an unwanted load to the body and therefore, it is important to find the least amount of protein that provides the maximal hypertrophic stimulus. Hence, research has focused on revealing the relationship between protein intake (dose) and its resulting stimulation of muscle protein synthesis (response). In addition to the protein amount, the protein digestibility and, hence, the availability of its constituent amino acids is decisive for the response. In this regard, recent studies have provided in-depth knowledge about the time-course of the muscle protein synthetic response dependent on the characteristics of the protein ingested. The effect of protein intake on muscle protein accretion can further be stimulated by prior exercise training. In the ageing population, physical training may counteract the development of “anabolic resistance” and restore the beneficial effect of protein feeding. Presently, our knowledge is based on measures obtained in standardized experimental settings or during long-term intervention periods. However, to improve coherence between these types of data and to further improve our knowledge of the effects of protein ingestion, other investigative approaches than those presently used are requested. Nutrients 2013-03-13 5 3 Review 10.3390/nu5030852 852 876 2072-6643 2013-03-13 doi: 10.3390/nu5030852 Kasper Dideriksen Søren Reitelseder Lars Holm http://www.mdpi.com/2072-6643/5/3/829 The development of obesity and insulin resistance has been extensively studied in the last decades, but the mechanisms underlying these alterations are still not completely understood. The gut microbiota has been identified as a potential contributor to metabolic diseases. It has been shown that obese individuals present different proportions of bacterial phyla compared with lean individuals, with an increase in Firmicutes and Actinobacteria and a decrease in Bacteroidetes. This alteration seems to interfere with intestinal permeability, increasing the absorption of lipopolysaccharide (LPS), which reaches circulation and initiates activation of Toll-like receptor (TLR) 4 and 2 and LPS receptor CD14, leading to increased activation of inflammatory pathways. With these activations, an impairment of the insulin signaling is observed, with decreased phosphorylation of the insulin receptor, insulin receptor substrate (IRS) and Akt, as well as increased inhibitory serine phosphorylation of IRS-1. Altered proportions of bacterial phyla have also been demonstrated to interfere with host’s biochemical pathways, increasing energy extraction and depot in adipose tissue. Therefore, understanding the mechanisms by which the alteration in the gut microbiota produces different signaling activations and phenotype changes may offer an interesting opportunity for the treatment of obesity and type 2 diabetes. Nutrients 2013-03-12 5 3 Review 10.3390/nu5030829 829 851 2072-6643 2013-03-12 doi: 10.3390/nu5030829 Andrea Caricilli Mario Saad http://www.mdpi.com/2072-6643/5/3/811 The objective of the present study was to assess factors predicting eating disorder risk in a sample of undergraduate students. A structured questionnaire was employed on a random sample (n = 1865) consisting of the following sections: demographics, SCOFF (Sick, Control, One stone, Fat, Food) questionnaire for screening eating disorders and the Achievement Anxiety Test and the Depression, Anxiety and Stress Scale. The students at risk for eating disorders (SCOFF score ≥2) were 39.7%. Eating disorder risk was more frequent in females, students with divorced parents, students who lived alone, students who were seeking a romantic relationship or were married, students who were at a post-secondary vocational institute/college (private-public) educational level and who were more likely to have marks under merit level. Also, the mean scores for the psychological factors of depression, stress and anxiety were higher in students with eating disorder risk. A logistic regression model was produced depicting that depression, stress, female gender, being married and searching for a romantic relationship were risk factors of having an eating disorder risk. The suggested psychological model examined with structural equation modelling signified the role of academic anxiety as an immediate precursor of general anxiety. Hence, college populations in Greece need organized infrastructures of nutrition health services and campaigns to assist in reducing the risk of eating disorders. Nutrients 2013-03-12 5 3 Article 10.3390/nu5030811 811 828 2072-6643 2013-03-12 doi: 10.3390/nu5030811 Konstantinos Fragkos Christos Frangos http://www.mdpi.com/2072-6643/5/3/788 A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits. Nutrients 2013-03-12 5 3 Article 10.3390/nu5030788 788 810 2072-6643 2013-03-12 doi: 10.3390/nu5030788 Daniel Roth Abdullah Mahmud Rubhana Raqib Evana Akhtar Robert Black Abdullah Baqui http://www.mdpi.com/2072-6643/5/3/771 Wheat is one of the most consumed cereal grains worldwide and makes up a substantial part of the human diet. Although government-supported dietary guidelines in Europe and the U.S.A advise individuals to eat adequate amounts of (whole) grain products per day, cereal grains contain “anti-nutrients,” such as wheat gluten and wheat lectin, that in humans can elicit dysfunction and disease. In this review we discuss evidence from in vitro, in vivo and human intervention studies that describe how the consumption of wheat, but also other cereal grains, can contribute to the manifestation of chronic inflammation and autoimmune diseases by increasing intestinal permeability and initiating a pro-inflammatory immune response. Nutrients 2013-03-12 5 3 Review 10.3390/nu5030771 771 787 2072-6643 2013-03-12 doi: 10.3390/nu5030771 Karin de Punder Leo Pruimboom http://www.mdpi.com/2072-6643/5/3/758 Selenium is an essential trace mineral of fundamental importance to human health. Much of its beneficial influence is attributed to its presence within selenoproteins, a group of proteins containing the rare amino acid selenocysteine. There are 25 known human selenoproteins including glutathione peroxidases, thioredoxin reductases and selenoproteins. Selenoprotein S (SEPS1) is an endoplasmic reticulum (ER) resident selenoprotein involved in the removal of misfolded proteins from the ER. SEPS1 expression can be induced by ER stress, an event that is associated with conformational disorders and occurs due to accumulation of misfolded proteins within the ER. Alpha-1 antitrypsin (AAT) deficiency, also known as genetic emphysema, is a conformational disorder in which the roles of ER stress, SEPS1 and selenium have been investigated. SEPS1 can relieve ER stress in an in vitro model of AAT deficiency by reducing levels of active ATF6 and inhibiting grp78 promoter- and NFκB activity; some of these effects are enhanced in the presence of selenium supplementation. Other studies examining the molecular mechanisms by which selenium mediates its anti-inflammatory effects have identified a role for prostaglandin 15d-PGJ2 in targeting NFκB and PPARγ. Together these ER stress-relieving and anti-inflammatory properties suggest a therapeutic potential for selenium supplementation in genetic emphysema. Nutrients 2013-03-11 5 3 Review 10.3390/nu5030758 758 770 2072-6643 2013-03-11 doi: 10.3390/nu5030758 Catherine Greene Roohi Chhabra Noel McElvaney http://www.mdpi.com/2072-6643/5/3/750 The objective of this project was to investigate the relationships between total and regional distribution of body fat and tissue lutein (L) and zeaxanthin (Z) status. Healthy men and women (N = 100; average age: 22.5 year, average BMI: 23.4 kg/m2) were evaluated. Total body and regional fat mass were assessed by dual-energy X-ray absorptiometry (Hologic Delphi A). Serum LZ was measured using reverse phase high-performance liquid chromatography, and retinal LZ (referred to as macular pigment optical density; MPOD) was measured using heterochromatic flicker photometry. Body fat percentage (total and regional) was inversely related to MPOD (p < 0.01) but no significant relationship was found for serum LZ. Higher body fat percentage, even within relatively healthy limits, is associated with lower tissue LZ status. The results indicate that adiposity may affect the nutritional state of the retina. Such links may be one of the reasons that obesity promotes age-related degenerative conditions of the retina. Nutrients 2013-03-08 5 3 Article 10.3390/nu5030750 750 757 2072-6643 2013-03-08 doi: 10.3390/nu5030750 Emily Bovier Richard Lewis Billy Hammond http://www.mdpi.com/2072-6643/5/3/725 The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. Nutrients 2013-03-07 5 3 Article 10.3390/nu5030725 725 749 2072-6643 2013-03-07 doi: 10.3390/nu5030725 Pamela Cassidy Heidi Fain James Cassidy Sally Tran Philip Moos Kenneth Boucher Russell Gerads Scott Florell Douglas Grossman Sancy Leachman http://www.mdpi.com/2072-6643/5/3/711 Previous studies have revealed that diabetic patients have a decline in immunity and an increased risk of infections, and this may be associated with poor micronutrient status. The aim of this study was to measure the effect of dietary supplements on risk of infection in patients with type 2 diabetes mellitus. One hundred patients with type 2 diabetes mellitus were randomly assigned to receive an oral dose of daily B-group vitamins and antioxidant vitamins (n = 50) or an identical placebo (n = 50) daily for 90 days. Patients had baseline, three and 12 month assessment for nutritional status, fruits and vegetables intake, physical activity and self-reported infections. Supplementation with antioxidants and B-group vitamins significantly increased the plasma concentration of vitamin E and folate and reduced homocysteine in the intervention group (p-values were 0.006, 0.001 and 0.657, respectively). The number of infections reported by the treatment group after three months of supplements was less than that reported by the placebo group, 9 (27%) vs. 15 (36%) (p = 0.623). Corresponding numbers of infections at 12 months were 25 (67.5%) and 27 (56.3%), respectively (p = 0.488). Up to 90% of the diabetic patients were either overweight or obese with a sedentary life style, and their body weight increased further during three months of follow up. The study showed that multivitamin supplements improved vitamin blood concentrations; however, this did not reduce the number of infections in diabetic patients. Nutrients 2013-03-05 5 3 Article 10.3390/nu5030711 711 724 2072-6643 2013-03-05 doi: 10.3390/nu5030711 Salah Gariballa Bachar Afandi Mamoon Haltem Javed Yassin Awad Alessa http://www.mdpi.com/2072-6643/5/3/700 Enshi is a high selenium (Se) region in Hubei, China, where human selenosis was observed between 1958 and 1963. This study investigated the daily dietary Se intake of residents in Shadi, a town located 72 km northeast of Enshi City, to assess the risk of human selenosis in the high Se area. Foods consumed typically by the local residents and their hair samples were analyzed for total Se concentration. Concentrations of Se in different diet categories were as follows: cereals: 0.96 ± 0.90 mg kg−1 DW in rice and 0.43 ± 0.55 mg kg−1 DW in corn; tuber: 0.28 ± 0.56 mg kg−1 in potato and 0.36 ± 0.12 mg kg−1 in sweet potato; vegetables: ranging from 0.23 ± 1.00 mg kg−1 in carrot to 1.57 ± 1.06 mg kg−1 in kidney bean; animal proteins: 1.99 ± 1.11 mg kg−1 in chicken and egg. Based on the food Se concentrations and the daily per-capita consumption, the estimated daily Se intake in Shadi was 550 ± 307 µg per capita. Moreover, the Se concentrations in the hairs of local adult residents were 3.13 ± 1.91 mg kg−1 (n = 122) and 2.21 ± 1.14 mg kg−1 (n = 122) for females and males, respectively, suggesting that females might be exposed to higher levels of Se from daily cooking. Although there was no human selenosis occurrence in recent years, the high level of the daily Se intake suggested that the potential risk of selenosis for local residents, especially females, might be a matter of concern. Nutrients 2013-03-05 5 3 Article 10.3390/nu5030700 700 710 2072-6643 2013-03-05 doi: 10.3390/nu5030700 Yang Huang Quanxin Wang Jin Gao Zhiqing Lin Gary Bañuelos Linxi Yuan Xuebin Yin http://www.mdpi.com/2072-6643/5/3/679 Short bowel syndrome (SBS) is a cause of significant morbidity and mortality in children. Probiotics, due to their beneficial effects on the gastrointestinal tract (e.g., improving gut barrier function, motility, facilitation of intestinal adaptation and decreasing pathogen load and inflammation) may have a therapeutic role in the management of SBS. To conduct a systematic review of the current evidence for the effects of probiotic supplementation in children with SBS, the standard Cochrane methodology for systematic reviews was used. The databases, Pubmed, Embase, ACTR, CENTRAL, and the international trial registry, and reference lists of articles were searched for randomised (RCT) or quasi-randomised controlled trials reporting on the use of probiotics in SBS. Our search revealed no RCTs on the use of probiotics in children with SBS. We found one small cross-over RCT (placebo controlled crossover clinical trial), one case control study and nine case reports on the use of probiotics in children with SBS. In the crossover RCT, there was no consistent effect on intestinal permeability (primary outcome) after supplementation with Lactobacillus rhamnosus (LGG) in nine children with SBS. The case control study (four cases: four controls) reported a trend for increase in height and weight velocity and improvement in non-clinical outcomes, such as gut flora, lymphocyte count and serum prealbumin. Five of the nine case reports showed that children (n = 12) with SBS were benefited (e.g., cessation of diarrhoea, improved faecal flora, weight gain and weaning from parenteral nutrition) by probiotic supplementation. The remaining four reported on the adverse effects, such as Lactobacillus sepsis (n = 3) and d-lactic acidosis (n = 2). There is insufficient evidence on the effects of probiotics in children with SBS. The safety and efficacy of probiotic supplementation in this high-risk cohort needs to be evaluated in large definitive trials. Nutrients 2013-03-05 5 3 Review 10.3390/nu5030679 679 699 2072-6643 2013-03-05 doi: 10.3390/nu5030679 Vudum Reddy Sanjay Patole Shripada Rao http://www.mdpi.com/2072-6643/5/3/663 Extracts, subfractions, isolated anthocyanins and isolated procyanidins B2, B5 and C1 from the berries and bark of Aronia melanocarpa were investigated for their antioxidant and enzyme inhibitory activities. Four different bioassays were used, namely scavenging of the diphenylpicrylhydrazyl (DPPH) radical, inhibition of 15-lipoxygenase (15-LO), inhibition of xanthine oxidase (XO) and inhibition of α-glucosidase. Among the anthocyanins, cyanidin 3-arabinoside possessed the strongest and cyanidin 3-xyloside the weakest radical scavenging and enzyme inhibitory activity. These effects seem to be influenced by the sugar units linked to the anthocyanidin. Subfractions enriched in procyanidins were found to be potent α-glucosidase inhibitors; they possessed high radical scavenging properties, strong inhibitory activity towards 15-LO and moderate inhibitory activity towards XO. Trimeric procyanidin C1 showed higher activity in the biological assays compared to the dimeric procyanidins B2 and B5. This study suggests that different polyphenolic compounds of A. melanocarpa can have beneficial effects in reducing blood glucose levels due to inhibition of α-glucosidase and may have a potential to alleviate oxidative stress. Nutrients 2013-03-04 5 3 Article 10.3390/nu5030663 663 678 2072-6643 2013-03-04 doi: 10.3390/nu5030663 Marie Bräunlich Rune Slimestad Helle Wangensteen Cato Brede Karl Malterud Hilde Barsett http://www.mdpi.com/2072-6643/5/3/651 Cow’s milk allergy (CMA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with about 80% naturally acquiring tolerance by the age of four years. However, recent studies suggest that the natural history of CMA is changing, with an increasing persistence until later ages. The pathogenesis of CMA, as well as oral tolerance, is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by CMA and healthy infants. These findings prompt the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells. The aim of this paper is to review what is currently known about the use of probiotics as dietary supplements in CMA. Nutrients 2013-03-01 5 3 Review 10.3390/nu5030651 651 662 2072-6643 2013-03-01 doi: 10.3390/nu5030651 Roberto Canani Margherita Di Costanzo http://www.mdpi.com/2072-6643/5/3/637 Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. Nutrients 2013-02-27 5 3 Article 10.3390/nu5030637 637 650 2072-6643 2013-02-27 doi: 10.3390/nu5030637 Md. Alam Kathleen Kauter Lindsay Brown http://www.mdpi.com/2072-6643/5/3/624 Selenium (Se) deficiency is associated with the occurrence of many diseases. However, excessive Se supplementation, especially with inorganic Se, can result in toxicity. Selenoproteins are the major forms of Se in vivo to exert its biological function. Expression of those selenoproteins, especially with the application of a newly developed system, is thus very important for studying the mechanism of Se in nutrition. The use of Chlamydomonas reinhardtii (C. reinhardtii) as a biological vector to express an heterogeneous protein is still at the initial stages of development. In order to investigate the possibility of using this system to express selenoproteins, human 15-KDa selenoprotein (Sep15), a small but widely distributed selenoprotein in mammals, was chosen for the expression platform test. Apart from the wild-type human Sep15 gene fragment, two Sep15 recombinants were constructed containing Sep15 open reading frame (ORF) and the selenocysteine insertion sequence (SECIS) element from either human Sep15 or C. reinhardtii selenoprotein W1, a highly expressed selenoprotein in this alga. Those Sep15-containing plasmids were transformed into C. reinhardtii CC-849 cells. Results showed that Sep15 fragments were successfully inserted into the nuclear genome and expressed Sep15 protein in the cells. The transgenic and wild-type algae demonstrated similar growth curves in low Se culture medium. To our knowledge, this is the first report on expressing human selenoprotein in green alga. Nutrients 2013-02-26 5 3 Article 10.3390/nu5030624 624 636 2072-6643 2013-02-26 doi: 10.3390/nu5030624 Qintang Hou Shi Qiu Qiong Liu Jing Tian Zhangli Hu Jiazuan Ni http://www.mdpi.com/2072-6643/5/2/608 Nutritional support of surgical and critically ill patients has undergone significant advances since 1936 when Studley demonstrated a direct relationship between pre-operative weight loss and operative mortality. The advent of total parenteral nutrition followed by the extraordinary progress in parenteral and enteral feedings, in addition to the increased knowledge of cellular biology and biochemistry, have allowed clinicians to treat malnutrition and improve surgical patient’s outcomes. We reviewed the literature for the current status of perioperative nutrition comparing parenteral nutrition with enteral nutrition. In a surgical patient with established malnutrition, nutritional support should begin at least 7–10 days prior to surgery. Those patients in whom eating is not anticipated beyond the first five days following surgery should receive the benefits of early enteral or parenteral feeding depending on whether the gut can be used. Compared to parenteral nutrition, enteral nutrition is associated with fewer complications, a decrease in the length of hospital stay, and a favorable cost-benefit analysis. In addition, many patients may benefit from newer enteral formulations such as Immunonutrition as well as disease-specific formulations. Nutrients 2013-02-21 5 2 Review 10.3390/nu5020608 608 623 2072-6643 2013-02-21 doi: 10.3390/nu5020608 Salim Abunnaja Andrea Cuviello Juan Sanchez http://www.mdpi.com/2072-6643/5/2/594 The present study investigated the effects of breast tumors on the blood and tissue distribution of essential trace mineral selenium (Se), and oxidative stress status of mice. Female 10-week-old BALB/cByJNarl mice were randomly assigned into control (CNL) and breast tumor-bearing (TB) groups. TB mice were injected subcutaneously into the right hind thigh with 5 × 106 EMT6 mouse mammary tumor cells. After 22 days, we measured Se concentrations, Se-dependent glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) products (indicator of oxidative stress) in plasma, various tissues, and plasma vascular endothelial growth factor (VEGF) concentrations. There were no significant differences in body weights and daily intake between both groups. Compared with the CNL group, TB mice have decreases in plasma Se concentrations and GPx activities, as well as higher plasma VEGF and MDA concentrations. Plasma Se concentrations were also negatively correlated with plasma MDA and VEGF concentrations. Furthermore, tissue Se concentrations and GPx activities in TB animals were lower; whereas the MDA concentrations higher in various tissues including liver, kidney, brain, lung, spleen, and thymic tissues. In conclusion, disruption of Se homeostasis critically reflects oxidative stress in target tissues, thus may increase the risk for progression of breast cancer and metastasis. Nutrients 2013-02-20 5 2 Article 10.3390/nu5020594 594 607 2072-6643 2013-02-20 doi: 10.3390/nu5020594 Chih-Hung Guo Simon Hsia Pei-Chung Chen http://www.mdpi.com/2072-6643/5/2/579 Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections. Nutrients 2013-02-19 5 2 Article 10.3390/nu5020579 579 593 2072-6643 2013-02-19 doi: 10.3390/nu5020579 Cristina González-Torres Haydeé González-Martínez Angel Miliar Oralia Nájera Jaime Graniel Verónica Firo Catalina Alvarez Edmundo Bonilla Leonor Rodríguez http://www.mdpi.com/2072-6643/5/2/565 The association of socioeconomic status (SES) with nutrient intake attracts public attention worldwide. In the current study, we examined the associations of SES with dietary intake of folate and health outcomes in general Japanese workers. This Japanese occupational cohort consisted off 2266 workers. SES was assessed by a self-administered questionnaire. Intakes of all nutrients were assessed with a validated, brief and self-administered diet history questionnaire (BDHQ). The degree of depressive symptoms was measured by the validated Japanese version of the K6 scale. Multiple linear regression and stratified analysis were used to evaluate the associations of intake with the confounding factors. Path analysis was conducted to describe the impacts of intake on health outcomes. Education levels and household incomes were significantly associated with intake of folate and depression scales (p < 0.05). After adjusting for age, sex and total energy intake, years of education significantly affect the folate intake (β = 0.117, p < 0.001). The structural equation model (SEM) shows that the indirect effect of folate intake is statistically significant and strong (p < 0.05, 56% of direct effect) in the pathway of education level to depression scale. Our study shows both education and income are significantly associated with depression scales in Japanese workers, and the effort to increase the folate intake may alleviate the harms of social disparities on mental health. Nutrients 2013-02-18 5 2 Article 10.3390/nu5020565 565 578 2072-6643 2013-02-18 doi: 10.3390/nu5020565 Koichi Miyaki Yixuan Song Setsuko Taneichi Akizumi Tsutsumi Hideki Hashimoto Norito Kawakami Masaya Takahashi Akihito Shimazu Akiomi Inoue Sumiko Kurioka Takuro Shimbo http://www.mdpi.com/2072-6643/5/2/552 Wild rice (WR) is a very nutritious grain that has been used to treat diabetes in Chinese medicinal practice. City diet (CD) is based on the diet consumed by Asian area residents in modern society, which is rich in saturated fats, cholesterol and carbohydrates. The present study was aimed at evaluating the effects of replacing white rice and processed wheat starch of CD with WR as the chief source of dietary carbohydrates on insulin resistance in rats fed with a high-fat/cholesterol diet. Except the rats of the low-fat (LF) diet group, the rats of the other three groups, including to high-fat/cholesterol (HFC) diet, CD and WR diet, were fed with high-fat/cholesterol diets for eight weeks. The rats fed with CD exhibited higher weight gain and lower insulin sensitivity compared to the rats consuming a HFC diet. However, WR suppressed high-fat/cholesterol diet-induced insulin resistance. WR decreased liver homogenate triglyceride and free fatty acids levels, raised serum adiponectin concentration and reduced serum lipocalin-2 and visfatin concentrations. In addition, the WR diet potently augmented the relative expressions of adiponectin receptor 2, peroxisome proliferator-activated receptors, alpha and gamma, and abated relative expressions of leptin and lipocalin-2 in the tissues of interest. These findings indicate that WR is effective in ameliorating abnormal glucose metabolism and insulin resistance in rats, even when the diet consumed is high in fat and cholesterol. Nutrients 2013-02-15 5 2 Abstract 10.3390/nu5020552 552 564 2072-6643 2013-02-15 doi: 10.3390/nu5020552 Shufen Han Hong Zhang Liqiang Qin Chengkai Zhai http://www.mdpi.com/2072-6643/5/2/543 We studied the macular pigment ocular density (MPOD) in patients with early age macular degeneration (AMD) before and 1 year after nutritional supplementation with lutein and docosahexaenoic acid (DHA). Forty-four patients with AMD were randomly divided into two groups that received placebo (n = 21) or a nutritional supplement (n = 23, 12 mg of lutein and 280 mg of DHA daily). Heterochromatic flicker photometry was used to determine the MPOD. At baseline, the MPOD in AMD patients with placebo was 0.286 ± 0.017 meanwhile in AMD patients with supplementation it was 0.291 ± 0.016. One year later, the mean MPOD had increased by 0.059 in the placebo group and by 0.162 in patients receiving lutein and DHA. This difference between groups was significant (p < 0.05). Lutein and DHA supplementation is effective in increasing the MPOD and may aid in prevention of age related macular degeneration. Nutrients 2013-02-15 5 2 Brief Report 10.3390/nu5020543 543 551 2072-6643 2013-02-15 doi: 10.3390/nu5020543 Alfredo García-Layana Sergio Recalde Angel Alamán Patricia Robredo http://www.mdpi.com/2072-6643/5/2/525 The tripeptide glutathione (GSH) is the most abundant intracellular nonprotein thiol, and it is involved in many cellular functions including redox-homeostatic buffering. Cellular radiosensitivity has been shown to be inversely correlated to the endogenous level of GSH. On the other hand, controversy is raised with respect to its role in the field of radioprotection since GSH failed to provide consistent protection in several cases. Reports have been published that DNA repair in cells has a dependence on GSH. Subsequently, S-glutathionylation (forming mixed disulfides with the protein–sulfhydryl groups), a potent mechanism for posttranslational regulation of a variety of regulatory and metabolic proteins when there is a change in the celluar redox status (lower GSH/GSSG ratio), has received increased attention over the last decade. GSH, as a single agent, is found to affect DNA damage and repair, redox regulation and multiple cell signaling pathways. Thus, seemingly, GSH does not only act as a radioprotector against DNA damage induced by X-rays through glutathionylation, it may also act as a modulator of the DNA-repair activity. Judging by the number of publications within the last six years, it is obvious that the field of protein glutathionylation impinges on many aspects of biology, from regulation of protein function to roles of cell cycle and apoptosis. Aberrant protein glutathionylation and its association with cancer and other diseases is an area of increasing interest. Nutrients 2013-02-07 5 2 Review 10.3390/nu5020525 525 542 2072-6643 2013-02-07 doi: 10.3390/nu5020525 Anupam Chatterjee http://www.mdpi.com/2072-6643/5/2/509 Fish oil and conjugated linoleic acid (CLA) belong to a popular class of food supplements known as “fat supplements”, which are claimed to reduce muscle glycogen breakdown, reduce body mass, as well as reduce muscle damage and inflammatory responses. Sport athletes consume fish oil and CLA mainly to increase lean body mass and reduce body fat. Recent evidence indicates that this kind of supplementation may have other side-effects and a new role has been identified in steroidogenensis. Preliminary findings demonstrate that fish oil and CLA may induce a physiological increase in testosterone synthesis. The aim of this review is to describe the effects of fish oil and CLA on physical performance (endurance and resistance exercise), and highlight the new results on the effects on testosterone biosynthesis. In view of these new data, we can hypothesize that fat supplements may improve the anabolic effect of exercise. Nutrients 2013-02-07 5 2 Review 10.3390/nu5020509 509 524 2072-6643 2013-02-07 doi: 10.3390/nu5020509 Filippo Macaluso Rosario Barone Patrizia Catanese Francesco Carini Luigi Rizzuto Felicia Farina Valentina Di Felice