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1.  Metazoan Remaining Genes for Essential Amino Acid Biosynthesis: Sequence Conservation and Evolutionary Analyses 
Nutrients  2014;7(1):1-16.
Essential amino acids (EAA) consist of a group of nine amino acids that animals are unable to synthesize via de novo pathways. Recently, it has been found that most metazoans lack the same set of enzymes responsible for the de novo EAA biosynthesis. Here we investigate the sequence conservation and evolution of all the metazoan remaining genes for EAA pathways. Initially, the set of all 49 enzymes responsible for the EAA de novo biosynthesis in yeast was retrieved. These enzymes were used as BLAST queries to search for similar sequences in a database containing 10 complete metazoan genomes. Eight enzymes typically attributed to EAA pathways were found to be ubiquitous in metazoan genomes, suggesting a conserved functional role. In this study, we address the question of how these genes evolved after losing their pathway partners. To do this, we compared metazoan genes with their fungal and plant orthologs. Using phylogenetic analysis with maximum likelihood, we found that acetolactate synthase (ALS) and betaine-homocysteine S-methyltransferase (BHMT) diverged from the expected Tree of Life (ToL) relationships. High sequence conservation in the paraphyletic group Plant-Fungi was identified for these two genes using a newly developed Python algorithm. Selective pressure analysis of ALS and BHMT protein sequences showed higher non-synonymous mutation ratios in comparisons between metazoans/fungi and metazoans/plants, supporting the hypothesis that these two genes have undergone non-ToL evolution in animals.
doi:10.3390/nu7010001
PMCID: PMC4303824  PMID: 25545100
comparative genomics; essential amino acids; molecular evolution
2.  The Impact of Diet and Lifestyle on Gut Microbiota and Human Health 
Nutrients  2014;7(1):17-44.
There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented.
doi:10.3390/nu7010017
PMCID: PMC4303825  PMID: 25545101
diet; lifestyle; gut; microbiota; health
3.  Understanding How Commensal Obligate Anaerobic Bacteria Regulate Immune Functions in the Large Intestine 
Nutrients  2014;7(1):45-73.
The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases.
doi:10.3390/nu7010045
PMCID: PMC4303826  PMID: 25545102
intestinal microbiota; intestinal immune homeostasis; obligate anaerobic bacteria; Faecalibacterium prausnitzii; Bacteroides thetaiotaomicron; Bacteroides fragilis; Akkermansia muciniphila; segmented filamentous bacteria; dual-environment co-culture models
4.  Prevalence of Hyperhomocysteinemia in China: A Systematic Review and Meta-Analysis 
Nutrients  2014;7(1):74-90.
Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 μmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3–97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.
doi:10.3390/nu7010074
PMCID: PMC4303827  PMID: 25551247
hyperhomocysteinemia; prevalence; China; meta-analysis
5.  The Relationship between Serum 25-Hydroxyvitamin D Concentration, Cardiorespiratory Fitness, and Insulin Resistance in Japanese Men 
Nutrients  2014;7(1):91-102.
Here, we aim to investigate the independent and combined associations of serum 25-hydroxyvitamin D (25(OH)D) and cardiorespiratory fitness (CRF) with glucose metabolism. Fasting blood samples of 107 men aged 40–79 years were analyzed for 25(OH)D, glucose, insulin, glycated hemoglobin, and lipid profile. Homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated from the fasting concentrations of glucose and insulin. Visceral fat area (VFA) was determined by magnetic resonance imaging and CRF by measuring maximal oxygen uptake. Median 25(OH)D concentration was 36.3 nmol/L, while the prevalence of 25(OH)D deficiency was 74.8%. Participants with high CRF had significantly lower HOMA-IR, glycated hemoglobin, and insulin values than participants with low CRF (p < 0.05). Higher 25(OH)D concentration was strongly correlated with lower HOMA-IR and insulin values independent of VFA (p < 0.01) but significantly affected by CRF. In the high CRF group, participants with higher 25(OH)D concentration had lower HOMA-IR values than participants with low 25(OH)D concentration (p < 0.05). Higher 25(OH)D and CRF are crucial for reducing insulin resistance regardless of abdominal fat. In addition, higher 25(OH)D concentration may strengthen the effect of CRF on reducing insulin resistance in middle-aged and elderly Japanese men with high CRF.
doi:10.3390/nu7010091
PMCID: PMC4303828  PMID: 25551248
vitamin D; cardiorespiratory fitness; insulin resistance; visceral fat
6.  Hepcidin-25, Mean Corpuscular Volume, and Ferritin as Predictors of Response to Oral Iron Supplementation in Hemodialysis Patients 
Nutrients  2014;7(1):103-118.
The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients.
doi:10.3390/nu7010103
PMCID: PMC4303829  PMID: 25551249
anemia; ferritin; hemodialysis; hepcidin; iron; mean corpuscular volume
7.  Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction 
Nutrients  2014;7(1):119-152.
Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.
doi:10.3390/nu7010119
PMCID: PMC4303830  PMID: 25551250
diabetes; heart; IUGR; hypertension; maternal diet
8.  A Review of the Impact of Dietary Intakes in Human Pregnancy on Infant Birthweight 
Nutrients  2014;7(1):153-178.
Studies assessing maternal dietary intakes and the relationship with birthweight are inconsistent, thus attempting to draw inferences on the role of maternal nutrition in determining the fetal growth trajectory is difficult. The aim of this review is to provide updated evidence from epidemiological and randomized controlled trials on the impact of dietary and supplemental intakes of omega-3 long-chain polyunsaturated fatty acids, zinc, folate, iron, calcium, and vitamin D, as well as dietary patterns, on infant birthweight. A comprehensive review of the literature was undertaken via the electronic databases Pubmed, Cochrane Library, and Medline. Included articles were those published in English, in scholarly journals, and which provided information about diet and nutrition during pregnancy and infant birthweight. There is insufficient evidence for omega-3 fatty acid supplements’ ability to reduce risk of low birthweight (LBW), and more robust evidence from studies supplementing with zinc, calcium, and/or vitamin D needs to be established. Iron supplementation appears to increase birthweight, particularly when there are increases in maternal hemoglobin concentrations in the third trimester. There is limited evidence supporting the use of folic acid supplements to reduce the risk for LBW; however, supplementation may increase birthweight by ~130 g. Consumption of whole foods such as fruit, vegetables, low-fat dairy, and lean meats throughout pregnancy appears beneficial for appropriate birthweight. Intervention studies with an understanding of optimal dietary patterns may provide promising results for both maternal and perinatal health. Outcomes from these studies will help determine what sort of dietary advice could be promoted to women during pregnancy in order to promote the best health for themselves and their baby.
doi:10.3390/nu7010153
PMCID: PMC4303831  PMID: 25551251
maternal nutrition; birthweight; undernutrition; overweight; nutrients; dietary patterns
9.  Piper and Vismia Species from Colombian Amazonia Differentially Affect Cell Proliferation of Hepatocarcinoma Cells 
Nutrients  2014;7(1):179-195.
There is an increasing interest to identify plant-derived natural products with antitumor activities. In this work, we have studied the effects of aqueous leaf extracts from Amazonian Vismia and Piper species on human hepatocarcinoma cell toxicity. Results showed that, depending on the cell type, the plants displayed differential effects; thus, Vismia baccifera induced the selective killing of HepG2, while increasing cell growth of PLC-PRF and SK-HEP-1. In contrast, these two last cell lines were sensitive to the toxicity by Piper krukoffii and Piper putumayoense, while the Piperaceae did not affect HepG2 growth. All the extracts induced cytotoxicity to rat hepatoma McA-RH7777, but were innocuous (V. baccifera at concentrations < 75 µg/mL) or even protected cells from basal death (P. putumayoense) in primary cultures of rat hepatocytes. In every case, cytotoxicity was accompanied by an intracellular accumulation of reactive oxygen species (ROS). These results provide evidence for the anticancer activities of the studied plants on specific cell lines and suggest that cell killing could be mediated by ROS, thus involving mechanisms independent of the plants free radical scavenging activities. Results also support the use of these extracts of the Vismia and Piper genera with opposite effects as a model system to study the mechanisms of the antitumoral activity against different types of hepatocarcinoma.
doi:10.3390/nu7010179
PMCID: PMC4303832  PMID: 25558904
antioxidant activity; free radical; polyphenol; hepatoma cell line; cell cycle arrest; flow cytometry; superoxide dismutase; catalase
10.  Heart Rate Variability and Cognitive Function Following a Multi-Vitamin and Mineral Supplementation with Added Guarana (Paullinia cupana) 
Nutrients  2014;7(1):196-208.
The aim of this study was to assess cognitive performance and heart rate variability (HRV) following the ingestion of either a multi-vitamin-mineral preparation supplemented with 300 mg guarana (Ac); a caffeine supplement (C) or a placebo supplement (Pl). Fifty-six subjects took part in a randomized, double-blind crossover design, consisting of three experimental sessions ran on a different day. Cognitive performance was assessed using a go/no-go task and a simple reaction time (SRT) task. HRV was assessed in the time domain (RMSSD) and in the frequency domain (HF) and cognitive tasks were performed before ingestion, 15 min after ingestion and then every 15 min over the course of 3 h. Responses were faster (without change in accuracy) when the go/no-go task was performed between 30 and 90 min after ingestion of Ac (4.6% ± 0.8%, p < 0.05). No effect was observed on SRT task. A significant decrease in HRV was observed during the first hour under C and Pl, whereas HRV remained stable under Ac. The results suggest that the ingestion of a multi-vitamin-mineral with added guarana improves decision-making performance and is accompanied by a stable autonomic nervous system regulation during the first hour.
doi:10.3390/nu7010196
PMCID: PMC4303833  PMID: 25558905
guarana; reaction time; decision-making; caffeine; heart rate variability
11.  Energy Balance of Triathletes during an Ultra-Endurance Event 
Nutrients  2014;7(1):209-222.
The nutritional strategy during an ultra-endurance triathlon (UET) is one of the main concerns of athletes competing in such events. The purpose of this study is to provide a proper characterization of the energy and fluid intake during real competition in male triathletes during a complete UET and to estimate the energy expenditure (EE) and the fluid balance through the race. Methods: Eleven triathletes performed a UET. All food and drinks ingested during the race were weighed and recorded in order to assess the energy intake (EI) during the race. The EE was estimated from heart rate (HR) recordings during the race, using the individual HR-oxygen uptake (Vo2) regressions developed from three incremental tests on the 50-m swimming pool, cycle ergometer, and running treadmill. Additionally, body mass (BM), total body water (TBW) and intracellular (ICW) and extracellular water (ECW) were assessed before and after the race using a multifrequency bioimpedance device (BIA). Results: Mean competition time and HR was 755 ± 69 min and 137 ± 6 beats/min, respectively. Mean EI was 3643 ± 1219 kcal and the estimated EE was 11,009 ± 664 kcal. Consequently, athletes showed an energy deficit of 7365 ± 1286 kcal (66.9% ± 11.7%). BM decreased significantly after the race and significant losses of TBW were found. Such losses were more related to a reduction of extracellular fluids than intracellular fluids. Conclusions: Our results confirm the high energy demands of UET races, which are not compensated by nutrient and fluid intake, resulting in a large energy deficit.
doi:10.3390/nu7010209
PMCID: PMC4303834  PMID: 25558906
energy balance; triathlon; energy expenditure; energy intake; macronutrient consumption; endurance; body water
12.  Hormonal and Dietary Characteristics in Obese Human Subjects with and without Food Addiction 
Nutrients  2014;7(1):223-238.
The concept of food addiction (FA) is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO) matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight), the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat) and the percent calorie intake from fat and carbohydrates (g/kg) was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium), fat and its components (such as saturated, monounsaturated and trans fat), omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.
doi:10.3390/nu7010223
PMCID: PMC4303835  PMID: 25558907
food addiction; gut hormones; neuropeptides; adipokines; micro-/macro-nutrient intake
13.  Fucoidan Supplementation Improves Exercise Performance and Exhibits Anti-Fatigue Action in Mice 
Nutrients  2014;7(1):239-252.
Fucoidan (FCD) is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group) were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002) and endurance swimming time (p = 0.0195) in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001) and ammonia (p = 0.0025), and also an increase in glucose level (p < 0.0001) after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.
doi:10.3390/nu7010239
PMCID: PMC4303836  PMID: 25558908
brown seaweed extract; exercise performance; forelimb grip strength
14.  Evaluation of Riboflavin Intakes and Status of 20–64-Year-Old Adults in South Korea 
Nutrients  2014;7(1):253-264.
A recent Korea National Health and Nutrition Survey indicated inadequate riboflavin intake in Koreans, but there is limited research regarding riboflavin status in South Korea. The purpose of this study was to determine riboflavin intake and status of Korean adults. Three consecutive 24-h food recalls were collected from 412 (145 men and 267 women) healthy adults, aged 20–64 years, living in South Korea and urine samples were collected from 149 subjects of all subjects. The dietary and total (dietary plus supplemental) riboflavin intake was 1.33 ± 0.34 and 2.87 ± 6.29 mg/day, respectively. Approximately 28% of the subjects consumed total riboflavin less than the Estimated Average Requirement. Urinary riboflavin excretion was 205.1 ± 190.1 μg/g creatinine. Total riboflavin intake was significantly positively correlated to the urinary riboflavin excretion. (r = 0.17171, p = 0.0363). About 11% of the Korean adults had urinary riboflavin <27 μg/g creatinine indicating a riboflavin deficiency and 21% had low status of riboflavin (27 μg/g creatinine ≤ urinary riboflavin < 80 μg/g creatinine). Thus, one-third of Korean adults in this study had inadequate riboflavin status. In some adults in Korea, consumption of riboflavin-rich food sources should be encouraged.
doi:10.3390/nu7010253
PMCID: PMC4303837  PMID: 25558909
riboflavin intake; riboflavin status; urinary excretion; riboflavin supplements; Korean adults
15.  Nutritional Interventions in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: A Narrative Review 
Nutrients  2015;7(1):265-276.
The present review aimed to define the role of nutritional interventions in the prevention and treatment of malnutrition in HNC patients undergoing CRT as well as their impact on CRT-related toxicity and survival. Head and neck cancer patients are frequently malnourished at the time of diagnosis and prior to the beginning of treatment. In addition, chemo-radiotherapy (CRT) causes or exacerbates symptoms, such as alteration or loss of taste, mucositis, xerostomia, fatigue, nausea and vomiting, with consequent worsening of malnutrition. Nutritional counseling (NC) and oral nutritional supplements (ONS) should be used to increase dietary intake and to prevent therapy-associated weight loss and interruption of radiation therapy. If obstructing cancer and/or mucositis interfere with swallowing, enteral nutrition should be delivered by tube. However, it seems that there is not sufficient evidence to determine the optimal method of enteral feeding. Prophylactic feeding through nasogastric tube or percutaneous gastrostomy to prevent weight loss, reduce dehydration and hospitalizations, and avoid treatment breaks has become relatively common. Compared to reactive feeding (patients are supported with oral nutritional supplements and when it is impossible to maintain nutritional requirements enteral feeding via a NGT or PEG is started), prophylactic feeding does not offer advantages in terms of nutritional outcomes, interruptions of radiotherapy and survival. Overall, it seems that further adequate prospective, randomized studies are needed to define the better nutritional intervention in head and neck cancer patients undergoing chemoradiotherapy.
doi:10.3390/nu7010265
PMCID: PMC4303838  PMID: 25569622
head and neck cancer; chemoradiotherapy; malnutrition; nutrition; nutritional counseling; oral nutritional supplements; enteral nutrition; gastrostomy
16.  Effects of Black Adzuki Bean (Vigna angularis) Extract on Proliferation and Differentiation of 3T3-L1 Preadipocytesinto Mature Adipocytes 
Nutrients  2015;7(1):277-292.
The aim of this work was to investigate the effects of black adzuki bean (BAB) extract on adipocytes, and to elucidate the cellular mechanisms. In order to examine the proliferation of preadipocytes and differentiating adipocytes, cell viability and DNA content were measured over a period of time. Lipid accumulation during cell differentiation and the molecular mechanisms underlying the effects of BAB on the transcriptional factors involved, with their anti-adipogenic effects, were also identified. We observed that BAB exhibits anti-adipogenic effects through the inhibition of proliferation, thereby lowering mRNA expression of C/EBPβ and suppressing adipogenesis during the early stage of differentiation. This, in turn, resulted in a reduction of TG accumulation in a dose- and time-dependent manner. Treating the cells with BAB not only suppressed the adipogenesis-associated key transcription factors PPARγ and C/EBPα but also significantly decreased the mRNA expression of GLUT4, FABP4, LPL and adiponectin. The expression of lipolytic genes like ATGL and HSL were higher in the treatment group than in the control. Overall, the black adzuki bean extract demonstrated an anti-adipogenic property, which makes it a potential dietary supplement for attenuation of obesity.
doi:10.3390/nu7010277
PMCID: PMC4303839  PMID: 25569623
adzuki bean; Vigna angularis; 3T3-L1; obesity; adipocyte; black bean
17.  Milk Consumption Following Exercise Reduces Subsequent Energy Intake in Female Recreational Exercisers 
Nutrients  2015;7(1):293-305.
The aim of this study was to evaluate the effects of skimmed milk as a recovery drink following moderate–vigorous cycling exercise on subsequent appetite and energy intake in healthy, female recreational exercisers. Utilising a randomised cross-over design, nine female recreational exercisers (19.7 ± 1.3 years) completed a V˙O2peak test followed by two main exercise trials. The main trials were conducted following a standardised breakfast. Following 30 min of moderate-vigorous exercise (65% V˙O2peak), either 600 mL of skimmed milk or 600 mL of orange drink (475 mL orange juice from concentrate, 125 mL water), which were isoenergetic (0.88 MJ), were ingested, followed 60 min later with an ad libitum pasta meal. Absolute energy intake was reduced 25.2% ± 16.6% after consuming milk compared to the orange drink (2.39 ± 0.70 vs. 3.20 ± 0.84 MJ, respectively; p = 0.001). Relative energy intake (in relation to the energy content of the recovery drinks and energy expenditure) was significantly lower after milk consumption compared to the orange drink (1.49 ± 0.72 vs. 2.33 ± 0.90 MJ, respectively; p = 0.005). There were no differences in AUC (× 1 h) subjective appetite parameters (hunger, fullness and desire to eat) between trials. The consumption of skimmed milk following 30 min of moderate-vigorous cycling exercise reduces subsequent energy intake in female recreational exercisers.
doi:10.3390/nu7010293
PMCID: PMC4303840  PMID: 25569624
females; milk; energy intake; subjective appetite; cycling exercise
18.  Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model 
Nutrients  2015;7(1):306-320.
Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.
doi:10.3390/nu7010306
PMCID: PMC4303841  PMID: 25569625
H. pylori; curcumin; nutritional approach; secondary prevention; mouse model
19.  Molecular Targets of Naturopathy in Cancer Research: Bridge to Modern Medicine 
Nutrients  2015;7(1):321-334.
The relevance of naturopathy (defined as the practice of medicine for the treatment of human diseases with natural agents) in human cancer is beginning to be appreciated, as documented by renewed interest in nutraceutical research, the natural anticancer agents of dietary origin. Because of their pleiotropic effects and the ability to modulate multiple signaling pathways, which is a good attribute of natural agents, nutraceuticals have frequently been demonstrated to re-sensitize drug-resistant cancers. The effectiveness of nutraceuticals can be further enhanced if the tools for the relative assessment of their molecular targets are readily available. Such information can be critical for determining their most effective uses. Here, we discuss the anticancer potential of nutraceuticals and the associated challenges that have interfered with their translational potential as a naturopathic approach for the management of cancers. In the years to come, an efficient screening and assessment of molecular targets will be the key to make rapid progress in the area of drug design and discovery, especially focusing on evidence-based development of naturopathy for the treatment of human malignancies.
doi:10.3390/nu7010321
PMCID: PMC4303842  PMID: 25569626
cancer; naturopathy; nutraceuticals
20.  Obesity Promotes Alterations in Iron Recycling 
Nutrients  2015;7(1):335-348.
Hepcidin is a key hormone that induces the degradation of ferroportin (FPN), a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD) modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1), FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER) stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.
doi:10.3390/nu7010335
PMCID: PMC4303843  PMID: 25569627
hepcidin; ferroportin; ER stress; obesity; iron; bioavailability
21.  Acknowledgement to Reviewers of Nutrients in 2014 
Nutrients  2015;7(1):349-359.
doi:10.3390/nu7010349
PMCID: PMC4303844
22.  Placental Adaptations in Growth Restriction 
Nutrients  2015;7(1):360-389.
The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.
doi:10.3390/nu7010360
PMCID: PMC4303845  PMID: 25580812
placental morphology; vascularity; substrate transport; IUGR
23.  Inclusion of Fermented Foods in Food Guides around the World 
Nutrients  2015;7(1):390-404.
Fermented foods have been a well-established part of the human diet for thousands of years, without much of an appreciation for, or an understanding of, their underlying microbial functionality, until recently. The use of many organisms derived from these foods, and their applications in probiotics, have further illustrated their impact on gastrointestinal wellbeing and diseases affecting other sites in the body. However, despite the many benefits of fermented foods, their recommended consumption has not been widely translated to global inclusion in food guides. Here, we present the case for such inclusion, and challenge health authorities around the world to consider advocating for the many benefits of these foods.
doi:10.3390/nu7010390
PMCID: PMC4303846  PMID: 25580813
food guides; world; fermented foods; fermentation; benefits; probiotics
24.  An Investigation into the Association between DNA Damage and Dietary Fatty Acid in Men with Prostate Cancer 
Nutrients  2015;7(1):405-422.
Prostate cancer is a growing problem in New Zealand and worldwide, as populations adopt a Western style dietary pattern. In particular, dietary fat is believed to be associated with oxidative stress, which in turn may be associated with cancer risk and development. In addition, DNA damage is associated with the risk of various cancers, and is regarded as an ideal biomarker for the assessment of the influence of foods on cancer. In the study presented here, 20 men with prostate cancer adhered to a modified Mediterranean style diet for three months. Dietary records, blood fatty acid levels, prostate specific antigen, C-reactive protein and DNA damage were assessed pre- and post-intervention. DNA damage was inversely correlated with dietary adherence (p = 0.013) and whole blood monounsaturated fatty acids (p = 0.009) and oleic acid (p = 0.020). DNA damage was positively correlated with the intake of dairy products (p = 0.043), red meat (p = 0.007) and whole blood omega-6 polyunsaturated fatty acids (p = 0.015). Both the source and type of dietary fat changed significantly over the course of the dietary intervention. Levels of DNA damage were correlated with various dietary fat sources and types of dietary fat.
doi:10.3390/nu7010405
PMCID: PMC4303847  PMID: 25580814
DNA damage; Mediterranean style diet; fatty acids; prostate cancer
25.  Guidelines for Feeding Very Low Birth Weight Infants 
Nutrients  2015;7(1):423-442.
Despite the fact that feeding a very low birth weight (VLBW) neonate is a fundamental and inevitable part of its management, this is a field which is beset with controversies. Optimal nutrition improves growth and neurological outcomes, and reduces the incidence of sepsis and possibly even retinopathy of prematurity. There is a great deal of heterogeneity of practice among neonatologists and pediatricians regarding feeding VLBW infants. A working group on feeding guidelines for VLBW infants was constituted in McMaster University, Canada. The group listed a number of important questions that had to be answered with respect to feeding VLBW infants, systematically reviewed the literature, critically appraised the level of evidence, and generated a comprehensive set of guidelines. These guidelines form the basis of this state-of-art review. The review touches upon trophic feeding, nutritional feeding, fortification, feeding in special circumstances, assessment of feed tolerance, and management of gastric residuals, gastro-esophageal reflux, and glycerin enemas.
doi:10.3390/nu7010423
PMCID: PMC4303848  PMID: 25580815
feeding; very low birth weight; neonate; review

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