Nutrients, Volume 10, Issue 5 (May 2018) – 130 articles

Nutrition and health claims on foods can help consumers make healthier food choices. However, claims may have a ‘halo’ effect, influencing consumer perceptions of foods and increasing consumption. Evidence for these effects are typically demonstrated in experiments with small samples, limiting generalisability. The current study aimed to overcome this limitation through the use of a nationally representative survey. In a cross-sectional survey of 1039 adults across the island of Ireland, respondents were presented with three different claims (nutrition claim = “Low in fat”; health claim = “With plant sterols. Proven to lower cholesterol”; satiety claim = “Fuller for longer”) on four different foods (cereal, soup, lasagne, and yoghurt). Participants answered questions on perceived healthiness, tastiness, and fillingness of the products with different claims and also selected a portion size they would consume. Claims influenced fillingness perceptions of some of the foods. However, there was little influence of claims on tastiness or healthiness perceptions or the portion size selected. Psychological factors such as consumers’ familiarity with foods carrying claims and belief in the claims were the most consistent predictors of perceptions and portion size selection. Future research should identify additional consumer factors that may moderate the relationships between claims, perceptions, and consumption. Full article

Neurodegenerative disease Alzheimer’s disease (AD) is attracting growing concern because of an increasing patient population among the elderly. Tea consumption is considered a natural complementary therapy for neurodegenerative diseases. In this paper, epidemiological studies on the association between tea consumption and the reduced risk of AD are reviewed and the anti-amyloid effects of related bioactivities in tea are summarized. Future challenges regarding the role of tea in preventing AD are also discussed. Full article

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions. Full article

Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice (n = 9) for 6 or 13 days. An additional group of mice (n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice (n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor. Full article

Vascular calcification (VC) as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification. Therefore, more complex underlying processes involving physiochemical changes to mineral balance, vascular remodelling and perturbed hormonal responses such as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) are likely to contribute to VC. In particular, VC resulting from modifications to calcium, phosphate and vitamin D homeostasis has been recently elucidated. Notably, deregulation of vitamin D metabolism, dietary calcium intake and renal mineral handling are associated with imbalances in systemic calcium and phosphate levels and endothelial cell dysfunction, which can modulate both bone and soft tissue calcification. This review addresses the current understanding of VC pathophysiology, with a focus on the pathogenic role of vitamin D that has provided new insights into the mechanisms of VC. Full article

Cow’s milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from early life to adolescence, and Immunoglobulin E (IgE) milk reactivity, focusing on gender differences in a large, population-based birth cohort. Overall, 20.0% (537/2985) of children, with a comparable gender distribution, had early life milk-related symptoms. At 16y, approximately 2% (62/2985) children had persistent symptoms and high milk IgE levels (e.g., median at 4 years: 1.5 kU_A/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kU_A/L, 8y: 0.72 kU_A/L; 16 years: 1.1 kU_A/L). Also, at 16 years, approximately 6% of females and 3% of males without any previously reported symptoms reported adolescent-onset of symptoms (p < 0.001). Such symptoms were almost exclusively gastrointestinal symptoms and were not associated with detectable IgE. In conclusion, early life milk-related symptoms are common, although most cases are transient by 16 years. Twice as many females vs. males report adolescent-onset symptoms, and particularly gastrointestinal symptoms. Children with persistent symptoms have both a higher prevalence and higher milk IgE levels, as compared to other phenotypes. Full article

Predictive iron bioavailability (FeBio) methods aimed at evaluating the association between diet and body iron have been proposed, but few studies explored their validity and practical usefulness in epidemiological studies. In this cross-sectional study involving 127 women (18–42 years) with presumably steady-state body iron balance, correlations were checked among various FeBio estimates (probabilistic approach and meal-based and diet-based algorithms) and serum ferritin (SF) concentrations. Iron deficiency was defined as SF < 15 µg/L. Pearson correlation, Friedman test, and linear regression were employed. Iron intake and prevalence of iron deficiency were 10.9 mg/day and 12.6%. Algorithm estimates were strongly correlated (0.69≤ r ≥0.85; p < 0.001), although diet-based models (8.5–8.9%) diverged from meal-based models (11.6–12.8%; p < 0.001). Still, all algorithms underestimated the probabilistic approach (17.2%). No significant association was found between SF and FeBio from Monsen (1978), Reddy (2000), and Armah (2013) algorithms. Nevertheless, there was a 30–37% difference in SF concentrations between women stratified at extreme tertiles of FeBio from Hallberg and Hulthén (2000) and Collings’ (2013) models. The results demonstrate discordance of FeBio from probabilistic approach and algorithm methods while suggesting two models with best performances to rank individuals according to their bioavailable iron intakes. Full article

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with inefficient macro- and micronutrient metabolism, and alteration of circulating phospholipid compositions defines the signature of NAFLD. This current study aimed to assess the pattern of serum phospholipids in the spectrum of NAFLD, and its related comorbidities and genetic modifications. Methods: 97 patients with diagnosed NAFLD were recruited at a single center during 2013–2016. Based on histological and transient elastography assessment, 69 patients were divided into non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL) subgroups. 28 patients served as healthy controls. Serum phospholipids were determined by liquid-chromatography mass spectrometry (LC-MS/MS). Results: The total content of phosphatidylcholine (PC) and sphingomyelin in the serum was significantly increased in NAFL and NASH patients, compared to healthy controls. In addition, serum lysophospatidylethanolamine levels were significantly decreased in NAFL and NASH individuals. Circulating PC species, containing linoleic and α-linolenic acids, were markedly increased in NAFLD patients with hypertension, compared to NAFLD patients without hypertension. The pattern of phospholipids did not differ between NAFLD patients with diabetes and those without diabetes. However, NAFLD patients with hyperglycemia (blood glucose level (BGL) >100 mg/dL) exhibited significantly a higher amount of monounsaturated phosphatidylethanolamine than those with low blood glucose levels. In addition, NAFLD patients with proven GG-genotype of PNPLA3, who were at higher risk for the development of progressive disease with fibrosis, showed lower levels of circulating plasmalogens, especially 16:0, compared to those with CC- and CG-allele. Conclusions: Our extended lipidomic study presents a unique metabolic profile of circulating phospholipids associated with the presence of metabolic risk factors or the genetic background of NAFLD patients. Full article

Inflammation is thought to be partly responsible for metabolic syndrome (MetS). Recently, dietary inflammatory index (DII) was developed to calculate the overall inflammatory potential of a diet. The objective of this study was to investigate the association between DII and MetS, as well as MetS components, using nationally representative survey data. The study sample consisted of 9291 Korean adults (aged 19–65 years, 3682 men and 5609 women) who participated in the sixth (2013–2015) Korea National Health and Nutrition Examination Survey. DII values were calculated using 24-h dietary recall data. Multivariable-adjusted logistic regression analysis was performed to identify the association between DII and MetS by sex. In the multivariate logistic regression model, the top DII quartile (Q4), was positively associated with MetS prevalence in men (Q4 vs. Q1, OR = 1.40; 95% CI = 1.06–1.85; p for linear trend = 0.008) and in postmenopausal women (Q4 vs. Q1, OR = 1.67; 95% CI = 1.15–2.44; p for linear trend = 0.008). The top DII quartile was also positively associated with the prevalence of hyperglycemia in men and the prevalence of central obesity in postmenopausal women. Further studies using prospective cohorts are needed to identify the causal relationship between DII and MetS. Full article

The dry root of Angelica sinensis (Oliv.) Diels, also known as “female ginseng”, is a popular herbal drug amongst women, used to treat a variety of health issues and cardiovascular diseases. The aim of this study is to evaluate the detailed molecular mechanism for anti-inflammatory effects of Angelica sinensis root water extract (ASW). The anti-inflammatory effect of ASW on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages was evaluated by the tetrazolium-based colorimetric assay (MTT), Griess reagent assay, multiplex cytokine assay, real time reverse transcription polymerase chain reaction (RT-PCR), and Fluo-4 calcium assay. ASW restored cell viability in RAW 264.7 at concentrations of up to 200 µg/mL. ASW showed notable anti-inflammatory effects. ASW exhibited IC₅₀ = 954.3, 387.3, 191.7, 317.8, 1267.0, 347.0, 110.1, 573.6, 1171.0, 732.6, 980.8, 125.0, and 257.0 µg/mL for interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic activating factor (MCP)-1, regulated on activation, normal T cell expressed and secreted (RANTES), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), lipopolysaccharide-induced CXC chemokine (LIX), macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, IL-10, and intracellular calcium, respectively. Additionally, ASW inhibited the LPS-induced production of nitric oxide and the LPS-induced mRNA expression of CHOP (GADD153), Janus kinase 2 (JAK2), signal transducers and activators of transcription 1 (STAT1), first apoptosis signal receptor (FAS), and c-Fos, NOS2, and PTGS2 (COX2) in RAW 264.7 significantly (p < 0.05). Data suggest that ASW exerts an anti-inflammatory effect on LPS-induced RAW 264.7 via NO-bursting/calcium-mediated JAK-STAT pathway. Full article

Pre-exercise fluid intake is an important healthy behavior for maintaining athletes’ sports performances and health. However, athletes’ behavioral adherence to fluid intake and its underlying psychological mechanisms have not been investigated. This prospective study aimed to use a health psychology model that integrates the self-determination theory and the theory of planned behavior for understanding pre-exercise fluid intake among athletes. Participants (n = 179) were athletes from college sport teams who completed surveys at two time points. Baseline (Time 1) assessment comprised psychological variables of the integrated model (i.e., autonomous and controlled motivation, attitude, subjective norm, perceived behavioral control, and intention) and fluid intake (i.e., behavior) was measured prospectively at one month (Time 2). Path analysis showed that the positive association between autonomous motivation and intention was mediated by subjective norm and perceived behavioral control. Controlled motivation positively predicted the subjective norm. Intentions positively predicted pre-exercise fluid intake behavior. Overall, the pattern of results was generally consistent with the integrated model, and it was suggested that athletes’ pre-exercise fluid intake behaviors were associated with the motivational and social cognitive factors of the model. The research findings could be informative for coaches and sport scientists to promote athletes’ pre-exercise fluid intake behaviors. Full article

Novel and alternative options are being adopted to combat the initiation and progression of human cancers. One of the approaches is the use of molecules isolated from traditional medicinal herbs, edible dietary plants and seeds that play a pivotal role in the prevention/treatment of cancer, either alone or in combination with existing chemotherapeutic agents. Compounds that modulate these oncogenic processes are potential candidates for cancer therapy and may eventually make it to clinical applications. Diosgenin is a naturally occurring steroidal sapogenin and is one of the major bioactive compounds found in dietary fenugreek (Trigonella foenum-graecum) seeds. In addition to being a lactation aid, diosgenin has been shown to be hypocholesterolemic, gastro- and hepato-protective, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-cancer. Diosgenin has a unique structural similarity to estrogen. Several preclinical studies have reported on the pro-apoptotic and anti-cancer properties of diosgenin against a variety of cancers, both in in vitro and in vivo. Diosgenin has also been reported to reverse multi-drug resistance in cancer cells and sensitize cancer cells to standard chemotherapy. Remarkably, diosgenin has also been reported to be used by pharmaceutical companies to synthesize steroidal drugs. Several novel diosgenin analogs and nano-formulations have been synthesized with improved anti-cancer efficacy and pharmacokinetic profile. In this review we discuss in detail the multifaceted anti-cancer properties of diosgenin that have found application in pharmaceutical, functional food, and cosmetic industries; and the various intracellular molecular targets modulated by diosgenin that abrogate the oncogenic process. Full article

The burden of malnutrition in Indigenous people is a major health priority and this study’s aims are to understand health outcomes among Indigenous and non-Indigenous patients. This cohort study includes 608 medical inpatients in three regional hospitals. Participants were screened for malnutrition using the Subjective Global Assessment tool. Hospital length of stay, discharge destination, 30-day and six-month hospital readmission and survival were measured. Although no significant difference was observed between Indigenous participants who were malnourished or nourished (p = 0.120), malnourished Indigenous participants were more likely to be readmitted back into hospital within 30 days (Relative Risk (RR) 1.53, 95% CI 1.19–1.97, p = 0.002) and six months (RR 1.40, 95% Confidence Interval (CI) 1.05–1.88, p = 0.018), and less likely to be alive at six months (RR 1.63, 95% CI 1.20–2.21, p = 0.015) than non-Indigenous participants. Malnutrition was associated with higher mortality (Hazards Ratio (HR) 3.32, 95% CI 1.87–5.89, p < 0.001) for all participants, and independent predictors for six-month mortality included being malnourished (HR 2.10, 95% CI 1.16–3.79, p = 0.014), advanced age (HR 1.04, 95% CI 1.02–1.06, p = 0.001), increased acute disease severity (Acute Physiology and Chronic Health Evaluation score, HR 1.03, 95% CI 1.01–1.05, p = 0.002) and higher chronic disease index (Charlson Comorbidity Index, HR 1.36, 95% CI 1.16–3.79, p = 0.014). Malnutrition in regional Australia is associated with increased healthcare utilization and decreased survival. New approaches to malnutrition-risk screening, increased dietetic resourcing and nutrition programs to proactively identify and address malnutrition in this context are urgently required. Full article

The prevalence of obesity and associated metabolic disorders, including diabetes and cardiovascular disease, is rapidly becoming a severe global health problem. Recent reports have suggested that the alteration of the gut ecosystem through the consumption of probiotics and fermented foods, such as yogurt and Kimchi, can significantly impact obesity and Type 2 diabetes (T2D)-related biomarkers. In this study, we screened over 400 strains of lactic acid bacteria (LAB) that were isolated from fermented foods to identify potent anti-obesogenic and diabetic probiotics in vitro. Of the strains tested, Lactobacillus plantarum Ln4 (Ln4), which was obtained from napa cabbage kimchi, significantly reduced lipid accumulation and stimulated glucose uptake in 3T3-L1 adipocytes. Oral administration of Ln4 reduced weight gain and epididymal fat mass in mice fed on a high-fat diet (HFD). Total plasma triglyceride level was significantly lower in mice that were treated Ln4 as compared with mice fed HFD. The protein levels of adipokines such as C-reactive protein (CRP), insulin-like growth factor binding proteins-3 (IGFBP-3), and monocyte chemoattractant protein-1 (MCP-1) decreased in white adipose tissues of Ln4-treated mice. Furthermore, these mice exhibited a significant reduction of insulin resistance index (HOMA-IR) and the improvement of glucose tolerance (OGTT) and insulin response (ITT) following Ln4 administration. This was associated with changes in several hepatic gene expressions (increased mRNA levels of IRS2, Akt2, AMPK, LPL, and reduced CD36) that regulate glucose and lipid metabolism. Taken together, these results indicate that in vitro and in vivo Ln4 treatment attenuates diet-induced obesity and T2D biomarkers, highlighting the potential of Ln4 as a therapeutic probiotic agent for metabolic disorders. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. However, therapeutic options treating only its symptoms are very disappointing. Therefore there is an ongoing search for compounds capable of tackling the multi-dimensional features of PD. Recently natural polyphenols have gained great interest as potential therapeutic agents. Herein, we have attempted to summarize results obtained in different animal models demonstrating their neuroprotective effects. The in vivo findings presented below are supported by human subject data and reports regarding the ability of polyphenols to cross the blood-brain barrier. The beneficial effects of polyphenols are demonstrated by the results of behavioral examinations, mainly related to motor and cognitive capabilities, histopathological and immunohistochemical examination concerning the protection of dopaminergic neurons, analyses of dopamine and the concentration of its metabolites, as well as mechanistic studies regarding the modulation of oxidative stress, neuroinflammation, cellular iron management, proteinopathy, and additionally the regulation of signaling pathways. Importantly, data about brain distribution of the metabolic derivatives of the reviewed polyphenols are crucial for the justification of their nutritional intake in neuroprotective intervention, as well as for the identification of potential targets for a novel therapeutic approach to Parkinson’s disease. Full article

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. At diagnosis, the majority of patients have villous atrophy in the small bowel mucosa. The objective of this study was to investigate whether the presence or absence of villous atrophy at diagnosis affects the long-term prognosis of DH. Data were gathered from the patient records of 352 DH and 248 coeliac disease patients, and follow-up data via questionnaires from 181 DH and 128 coeliac disease patients on a gluten-free diet (GFD). Of the DH patients, 72% had villous atrophy when DH was diagnosed, and these patients were significantly younger at diagnosis compared to those with normal small bowel mucosa (37 vs. 54 years, p < 0.001). Clinical recovery on a GFD did not differ significantly between the DH groups, nor did current adherence to a GFD, the presence of long-term illnesses, coeliac disease-related complications or gastrointestinal symptoms, or quality of life. By contrast, the coeliac disease controls had more often osteopenia/osteoporosis, thyroid diseases, malignancies and current gastrointestinal symptoms compared to the DH patients. In conclusion, villous atrophy at the time of DH diagnosis does not have an impact on the clinical recovery or long-term general health of DH patients. Full article

Pregnant women in Asia, the Middle East, Africa and Latin America are at risk of vitamin D deficiency (VDD) and prevalence throughout these regions are among the highest, globally. Maternal VDD has been associated with increased risk of a number of adverse maternal and neonatal health outcomes, yet research from developing countries is limited. We assessed the associations of maternal VDD during pregnancy with adverse health outcomes by synthesizing the literature from observational studies conducted in developing countries. Six electronic databases were searched for English-language studies published between 2000 and 2017. Thirteen studies from seven countries were included in the review. Prevalence of VDD ranged from 51.3% to 100%. Six studies assessed both maternal and neonatal outcomes, four studies assessed only maternal outcomes and three studies assessed only neonatal outcomes. Ten studies showed at least one significant association between VDD and adverse maternal and/or neonatal health outcomes including pre-eclampsia (n = 3), gestational diabetes mellitus (n = 1), postpartum depression (n = 1), emergency cesarean section delivery (n = 1), low birth weight babies (n = 4), small for gestational age (n = 2), stunting (n = 1). However most of these studies (n = 6) also showed no association with multiple health outcomes. Vitamin D assessment methods, criteria applied to define VDD, season and trimester in which studies were conducted varied considerably across studies. In conclusion, this study highlights the need to improve maternal vitamin D status in developing countries in an effort to support best maternal and child health outcomes across these regions. Future research should focus on more unified approaches to vitamin D assessment and preventative approaches that may be embedded into already existing antenatal care settings. Full article

Cobalamin and folate are crucial micronutrients during infancy and they are required for growth and cognitive development. Due to the monotonous and predominantly vegetarian-based complementary feeding and poor maternal micronutrient status, infants from low- and middle-income countries are susceptible to cobalamin deficiency. However, data on plasma cobalamin and folate and the functional markers methylmalonic acid and total homocysteine from breastfed infants in Nepal are still needed. We collected plasma samples from 316 6–11-month-old breastfed infants with a length-for-age of less than minus one z-score and analyzed blood for plasma folate, cobalamin, methylmalonic acid and total homocysteine concentrations. Cobalamin deficiency (plasma cobalamin <148 pmol/L) was found among 11%, whereas 24% of the infants had plasma cobalamin concentrations between 148–221 pmol/L. Elevated total homocysteine (>10 µmol/L) and methylmalonic acid (>0.28 µmol/L) indicating functional cobalamin deficiency were found among 53% and 75% of the infants, respectively. Based on a combined indicator of cobalamin status, 58% were found to have low cobalamin status. However, folate deficiency (<10 nmol/L) was not found as the lowest value of plasma folate was 20.7 nmol/L. It is important to examine the extent to which poor cobalamin status during infancy has immediate or long-term consequences. Full article

The amount, composition, and sources of nutrition support provided to preterm infants is critical for normal growth and development, and particularly for structural and functional neurodevelopment. Although omega-3 long chain polyunsaturated fatty acids (LC-PUFA), and particularly docosahexanoic acid (DHA), are considered of particular importance, results from clinical trials with preterm infants have been inconclusive because of ethical limitations and confounding variables. A translational large animal model is needed to understand the structural and functional responses to DHA. Neurodevelopment of preterm pigs was evaluated in response to feeding formulas to term-equivalent age supplemented with DHA attached to phosphatidylserine (PS-DHA) or sunflower oil as the placebo. Newborn term pigs were used as a control for normal in utero neurodevelopment. Supplementing formula with PS-DHA increased weight of the brain, and particularly the cerebellum, at term-equivalent age compared with placebo preterm pigs (P’s < 0.10 and 0.05 respectively), with a higher degree of myelination in all regions of the brain examined (all p < 0.06). Brains of pigs provided PS-DHA were similar in weight to newborn term pigs. Event-related brain potentials and performance in a novel object recognition test indicated the PS-DHA supplement accelerated development of sensory pathways and recognition memory compared with placebo preterm pigs. The PS-DHA did not increase weight gain, but was associated with higher survival. The benefits of PS-DHA include improving neurodevelopment and possibly improvement of survival, and justify further studies to define dose-response relations, compare benefits associated with other sources of DHA, and understand the mechanisms underlying the benefits and influences on the development of other tissues and organ systems. Full article

Growth after preterm birth is an important determinant of long-term outcomes. Yet, many preterm infants suffer ex utero growth retardation. We evaluated effects of leucine and the metabolite, β-hydroxy β-methylbutyrate (HMB) on growth of preterm pigs, a previously-validated translational model for preterm infants. After 48 h of parenteral nutrition preterm pigs were fed for 6 to 7 days isocaloric formulas with different levels of protein (50 or 100 g/L) with leucine (10 g/L, 76 mM) or HMB (at 1.1 g/L, 4 mM) added to stimulate protein synthesis or with alanine (6.8 g/L; 76 mM) as the control. Rates of growth of pigs fed the low protein formula with alanine (3.4 ± 0.2% gain per day) or leucine (3.7 ± 0.2) exceeded that of pigs fed the high protein formula (2.8 ± 0.2, p = 0.02 for comparison with both low protein formulas; p = 0.01 compared with low protein + leucine). Supplementing the high protein formula with leucine or HMB did not increase growth relative to alanine (2.72 ± 0.20, 2.74 ± 0.27, and 2.52 ± 0.20, respectively). Small pigs (<700 g birth weight) grew slower during parenteral nutrition and had a more pronounced response to leucine. Females fed the high protein formulas grew faster than males, and particularly for small pigs (p < 0.05). Blood urea nitrogen values were lower for pigs fed the low versus the high protein formulas (p < 0.05). Leucine and HMB improved growth of preterm pigs fed low, but not high protein formulas, even after controlling for birth weight and sex, which independently correlated with growth rates. They offer an option to improve growth without increasing the amino acid load, with its attendant metabolic disadvantages. Full article

Background: Short successive periods of physical inactivity occur throughout life and contribute considerably to the age-related loss of skeletal muscle mass. The maintenance of muscle mass during brief periods of disuse is required to prevent functional decline and maintain metabolic health. Objective: To assess whether daily leucine supplementation during a short period of disuse can attenuate subsequent muscle loss in vivo in humans. Methods: Thirty healthy (22 ± 1 y) young males were exposed to a 7-day unilateral knee immobilization intervention by means of a full leg cast with (LEU, n = 15) or without (CON, n = 15) daily leucine supplementation (2.5 g leucine, three times daily). Prior to and directly after immobilization, quadriceps muscle cross-sectional area (computed tomography (CT) scan) and leg strength (one-repetition maximum (1-RM)) were assessed. Furthermore, muscle biopsies were taken in both groups before and after immobilization to assess changes in type I and type II muscle fiber CSA. Results: Quadriceps muscle cross-sectional area (CSA) declined in the CON and LEU groups (p < 0.01), with no differences between the two groups (from 7712 ± 324 to 7287 ± 305 mm² and from 7643 ± 317 to 7164 ± 328 mm²; p = 0.61, respectively). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the CON group and from 63 ± 3 to 55 ± 2 kg in the LEU group (main effect of time p < 0.01), with no differences between the groups (p = 0.052). Type I and II muscle fiber size did not change significantly over time, in both groups (p > 0.05). Conclusions: Free leucine supplementation with each of the three main meals (7.5 g/d) does not attenuate the decline of muscle mass and strength during a 7-day limb immobilization intervention. Full article

The aim of this study was to assess the effect of feeding high protein human milk fortifier (HMF) on growth in preterm infants. In this single-centre randomised trial, 60 infants born 28–32 weeks’ gestation were randomised to receive a higher protein HMF providing 1.8 g protein (n = 31) or standard HMF providing 1 g protein per 100 mL expressed breast milk (EBM) (n = 29). The primary outcome was rate of weight gain. Baseline characteristics were similar between groups. There was no difference between high and standard HMF groups for weight gain (mean difference (MD) −14 g/week; 95% CI −32, 4; p = 0.12), length gain (MD −0.01 cm/week; 95% CI −0.06, 0.03; p = 0.45) or head circumference gain (MD 0.007 cm/week; 95% CI −0.05, 0.06; p = 0.79), despite achieving a 0.7 g/kg/day increase in protein intake in the high protein group. Infants in the high protein group had a higher proportion of lean body mass at trial entry; however, there was no group by time effect on lean mass gains over the study. Increasing HMF protein content to 1.8 g per 100 mL EBM does not improve growth in preterm infants born 28–32 weeks’ gestation. Full article

The benefits of goat milk, fermented milks, and probiotics for the humans are well documented. In this study, a novel fermented goat milk was manufactured with the putative probiotic strain Lactobacillus plantarum C4 together with L. bulgaricus and Streptococcus thermophilus. Ultrafiltration was chosen as the skimmed milk concentration method because it produced the best viscosity and syneresis and a high casein content. The viability rate of all bacterial strains was >10⁷ cfu/mL, even after 5 weeks of storage or after in vitro gastrointestinal digestion, which is especially important for exertion of the probiotic strain functionalities. This fermented milk is also a good source of nutrients, having a low lactose and fat content, high protein proportion, and good mineral concentration. According to these data and the overall acceptability described by panelists, this fermented milk is a healthy dairy product comparable with commercially available fermented milks. Full article

Iron deficiency is reported as the most common nutrient deficiency worldwide. Due to rapid growth, infants are at particular risk for developing iron deficiency, which can easily progress to iron deficiency anemia (IDA), if not treated. The aim of this study was to determine the lasting effects of an early-life iron deficiency after a period of dietary iron repletion. Forty-two intact male pigs were fed, ad libitum, either control (CONT, 21.3 mg Fe/L) or iron-deficient (ID 2.72 mg Fe/L) milk replacer from postnatal day (PND) 2 to 32 (phase 1). From PND 33 to 61 (phase 2), all pigs were transitioned onto a series of industry-standard, iron-adequate diets. Blood was collected weekly from PND 7 to 28, and again on PND 35 and 56, and tissues were collected at either PND 32 or PND 61. At the end of phase 1, ID pigs exhibited reduced hematocrit (Hct; p < 0.0001) and hemoglobin (Hb; p < 0.0001) compared with CONT pigs, but neither Hct (p = 0.5968) nor Hb (p = 0.6291) differed between treatment groups after dietary iron repletion at the end of phase 2. Body weight gain was reduced (p < 0.0001) 58% at PND 32 in ID pigs compared with CONT pigs during phase 1, and this effect remained significant at the end of phase 2 (p = 0.0001), with ID pigs weighing 34% less than CONT pigs at PND 61. Analysis of peripheral protein and messenger RNA (mRNA) gene expression biomarkers yielded inconclusive results, as would be expected based on previous biomarker analyses across multiple species. These findings suggest that early-life iron status negatively influences blood parameters and growth performance, with dietary iron repletion allowing for full recovery of hematological outcomes, but not growth performance. Full article

Human milk provides immunoglobulins (Igs) that supplement the passive immune system of neonates; however, the extent of survival of these Igs during gastric digestion and whether this differs between preterm and term infants remains unknown. Human milk, and infant gastric samples at 2 h post-ingestion were collected from 15 preterm (23–32 week gestational age (GA)) mother-infant pairs and from 8 term (38–40 week of GA) mother-infant pairs within 7–98 days postnatal age. Samples were analyzed via ELISA for concentration of total IgA (secretory IgA (SIgA)/IgA), total secretory component (SC/SIgA/SIgM), total IgM (SIgM/IgM), and IgG as well as peptidomics. Total IgA concentration decreased by 60% from human milk to the preterm infant stomach and decreased by 48% in the term infant stomach. Total IgM and IgG concentrations decreased by 33% and 77%, respectively, from human milk to the term infant stomach but were stable in the preterm infant stomach. Release of peptides from all Ig isotypes in the term infant stomach was higher than in the preterm stomach. Overall, the stability of human milk Igs during gastric digestion is higher in preterm infant than in term infants, which could be beneficial for assisting the preterm infants’ immature immune system. Full article

Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin. Full article

Aim: Low circulating vitamin D levels are associated with gastric adenocarcinoma, but whether vitamin D levels are associated with premalignant gastric mucosal changes is unknown. Here, we determined associations between vitamin D levels and gastric incomplete intestinal metaplasia, a known gastric adenocarcinoma risk factor. Methods: This was a retrospective, unmatched, case-control study comparing serum 25-hydroxyvitamin D levels among subjects with gastric incomplete intestinal metaplasia (cases; n = 103) and those without gastric incomplete intestinal metaplasia (controls; n = 216). The 25-hydroxyvitamin D levels were categorized as normal (30–100 ng/dL), vitamin D insufficiency (VDi; 20–29 ng/dL), and vitamin D deficiency (VDd; <20 ng/dL). Using multivariable logistic regression, odds ratios (ORs) were calculated and adjusted to age, gender, ethnicity, body mass index, history of hypertension or diabetes mellitus, and timing of vitamin D collection to assess associations between 25-hydroxyvitamin D levels and gastric incomplete intestinal metaplasia. Results: A majority of case subjects were male, Hispanic, and did not have hypertension or diabetes mellitus. The average serum 25-hydroxyvitamin D level was significantly lower in the intestinal metaplasia group than the control group (19.7 ng/dL vs. 34.7 ng/dL; p < 0.001). Hypovitaminosis D was more common in subjects with incomplete intestinal metaplasia in a multivariable regression model (OR 54.1, 95% CI 21.8–134.3; p < 0.001). VDd (OR 129.0, 95% CI 43.7–381.2; p < 0.001) and VDi (OR 31.0, 95% CI 11.9–80.3; p < 0.001) were more common in patients with incomplete intestinal metaplasia than healthy subjects, with VDd slightly more prevalent than VDi (OR 4.0, 95% CI 1.7–9.6; p < 0.001). Conclusions: Vitamin D deficiency and insufficiency are more common in patients with gastric incomplete intestinal metaplasia than healthy subjects and may play a role in the development of premalignant phenotypes related to gastric adenocarcinoma. Full article

The greatest burden of cardiovascular disease is now carried by developing countries with cardiometabolic conditions such as metabolic syndrome, obesity and inflammation believed to be the driving force behind this epidemic. Dietary fiber is known to have protective effects against obesity, type 2 diabetes, cardiovascular disease and the metabolic syndrome. Considering the emerging prevalence of these cardiometabolic disease states across the epidemiologic transition, the objective of this study is to explore these associations of dietary fiber with cardiometabolic risk factors in four countries across the epidemiologic transition. We examined population-based samples of men and women, aged 25–45 of African origin from Ghana, Jamaica, the Seychelles and the USA. Ghanaians had the lowest prevalence of obesity (10%), while Jamaicans had the lowest prevalence of metabolic syndrome (5%) across all the sites. Participants from the US presented with the highest prevalence of obesity (52%), and metabolic syndrome (22%). Overall, the Ghanaians consumed the highest dietary fiber (24.9 ± 9.7 g), followed by Jamaica (16.0 ± 8.3 g), the Seychelles (13.6 ± 7.2 g) and the lowest in the USA (14.2 ± 7.1 g). Consequently, 43% of Ghanaians met the fiber dietary guidelines (14 g/1000 kcal/day), 9% of Jamaicans, 6% of Seychellois, and only 3% of US adults. Across all sites, cardiometabolic risk (metabolic syndrome, inflammation and obesity) was inversely associated with dietary fiber intake, such that the prevalence of metabolic syndrome was 13% for those in the lowest quartile of fiber intake, compared to 9% those in the highest quartile of fiber intake. Notably, twice as many of participants (38%) in the lowest quartile were obese compared to those in the highest quartile of fiber intake (18%). These findings further support the need to incorporate strategies and policies to promote increased dietary fiber intake as one component for the prevention of cardiometabolic risk in all countries spanning the epidemiologic transition. Full article

Obesity is a result of positive energy balance. The aim of this study was to measure (in crossover trials) the energy expenditure and oxidation of glucose and lipids, both at the fasting state and after an intake of meals with a varying macronutrient content, in normal-weight and overweight/obese people. In the study, 46 healthy adult males (23 with normal body weight and 23 overweight/obese), aged 21–58, were examined. During two consecutive visits, subjects received isocaloric standardized meals (450 kcal) with different content of basic nutrients. Resting metabolic rate and carbohydrate and fat utilization were evaluated during the fasting state and postprandially, using an indirect calorimetry method. Energy expenditure was higher in people with normal body weight and slightly higher after the high-carbohydrate meal. In overweight/obese people, increased expenditure was noted after normo-carbohydrate meal intake. The high-fat meal induced lower postprandial thermal response compared to a high-carbohydrate meal, both in people with normal body weight and in overweight/obese men. Glucose utilization was higher after the high-carbohydrate meal, and it was higher in the normal body weight group than in overweight/obese people. In addition, overweight/obese people showed a lower level of fatty acid oxidation under fasting conditions which, together with limited ability to oxidize energy substrates, depending on their availability, indicates that these people are characterized by lower metabolic flexibility. Full article