Nutrients, Volume 12, Issue 1 (January 2020) – 273 articles

Background: Since no treatment exists for children suffering from upper respiratory tract infections (URTIs) without immunological disorders, we searched for a possible tool to improve the health of these children. Aim: We evaluated whether dietary advice (based on food matrix and food synergy), including standard supportive care, can decrease the number and duration of URTIs in children with recurrent URTIs. Design and Setting: This study was a multicenter randomized controlled trial in two pediatric outpatient clinics in the Netherlands, with 118 children aged one to four years with recurrent URTIs. The dietary advice group received dietary advice plus standard supportive care, while the control group received standard supportive care alone for six months. The dietary advice consisted of green vegetables five times per week, beef three times per week, 300 mL whole milk per day, and whole dairy butter on bread every day. Portion sizes were age-appropriate. Results and Conclusion: Children in the dietary advice group had 4.8 (1.6–9.5) days per month with symptoms of an URTI in the last three months of the study, compared to 7.7 (4.0–12.3) in the control group (p = 0.028). The total number of URTIs during the six-month study period was 5.7 (±0.55) versus 6.8 (±0.49), respectively (p = 0.068). The use of antibiotics was significantly reduced in the dietary advice group, as well as visits to a general practitioner, thereby possibly reducing healthcare costs. The results show a reduced number of days with symptoms of a URTI following dietary advice. The number of infections was not significantly reduced. Full article

The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We hypothesised that unfiltered VOO could possess low molecular weight peptides with antihypertensive activity. We produced unfiltered VOO and obtained a water-soluble peptide extract from it. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction was analysed by nanoscale liquid chromatography-Orbitrap coupled with tandem mass spectrometry and de novo sequencing. We selected 23 peptide sequences containing between 6 and 9 amino acids and molecular masses ranging 698–1017 Da. Those peptides were chemically synthesised and their angiotensin-converting enzyme (ACE) inhibitory activity was studied in vitro. Seven peptides showed a strong activity, with half maximal inhibitory concentration (IC50) <10 µm. The antihypertensive effects of the four most active synthesised ACE inhibitor peptides were studied in spontaneously hypertensive rats (SHR). Acute oral administration of synthetic peptides RDGGYCC and CCGNAVPQ showed antihypertensive activity in SHR. We conclude that unfiltered VOO naturally contains low molecular weight peptides with specific ACE inhibitory activity and antihypertensive effects in SHR. Full article

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can induce chronic inflammation, ultimately triggering disease progression. Pigment epithelium-derived factor (PEDF) is a secreted, multifunctional glycoprotein with lipid metabolic activities. PEDF promotes lipolysis through binding to adipose triglyceride lipase (ATGL), a key enzyme for triglyceride breakdown. In the current study, we aimed to delineate how changes in PEDF expression affect hepatic lipid accumulation. Our data revealed that hepatic PEDF was downregulated in a mouse NAFLD model. We further showed that decreased PEDF levels in hepatocytes in vitro resulted in elevated fatty acid uptake and lipid droplet formation, with concomitant upregulation of fatty acid transport proteins CD36 and fatty acid binding protein 1 (FABP1). RNA sequencing analysis of PEDF knocked down hepatocytes revealed an alteration in gene expression profile toward lipid accumulation. Additionally, decreased PEDF promotes mobilization of fatty acids, an observation distinct from blocking ATGL activity. Taken together, our data suggest that hepatic PEDF downregulation causes molecular changes that favor triglyceride accumulation, which may further lead to NAFLD progression. Full article

Periodontitis is a polymicrobial infectious disease that leads to inflammation of the gingiva, resulting in teeth loss by various causes such as inflammation-mediated bone resorption. Recently, many investigators have reported that the periodontitis resulting from persistent low-grade infection of Gram-negative bacteria such as Porphyromonas gingivalis (Pg) is associated with increased atherosclerosis, diabetes mellitus, and other systemic diseases through blood stream. On the other hand, carotenoids belong among phytochemicals that are responsible for different colors of the foods. It is important to examine whether carotenoids are effective to the inhibition of periodontal infection/inflammation cascades. This review summarizes the advanced state of knowledge about suppression of periodontal infection by several carotenoids. A series of findings suggest that carotenoids intake may provide novel strategy for periodontitis treatment, although further study will be needed. Full article

Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients’ nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the alveolus after tooth extraction. This scoping review aims to summarize the role of dietary supplements in optimizing osseointegration after implant insertion surgery. A technical expert panel (TEP) of 11 medical specialists with expertise in oral surgery, bone metabolism, nutrition, and orthopedic surgery performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP identified micronutrients from the “European Union (EU) Register of nutrition and health claims made on foods” that have a relationship with bone and tooth health, and planned a PubMed search, selecting micronutrients previously identified as MeSH (Medical Subject Headings) terms and adding to each of them the words “dental implants” and “osseointegration”. The TEP identified 19 studies concerning vitamin D, magnesium, resveratrol, vitamin C, a mixture of calcium, magnesium, zinc, and vitamin D, and synthetic bone mineral. However, several micronutrients are non-authorized by the “EU Register on nutrition and health claims” for improving bone and/or tooth health. Our scoping review suggests a limited role of nutraceuticals in promoting osseointegration of dental implants, although, in some cases, such as for vitamin D deficiency, there is a clear link among their deficit, reduced osseointegration, and early implant failure, thus requiring an adequate supplementation. Full article

Selenium is an essential micronutrient commonly deficient in human populations. Selenium deficiency increases the risks of pregnancy complications; however, the long-term impact of selenium deficiency on offspring disease remains unclear. This study investigates the effects of selenium deficiency during pregnancy on offspring metabolic function. Female C57BL/6 mice were allocated to control (>190 μg selenium/kg, n = 8) or low selenium (<50 μg selenium/kg, n = 8) diets prior to mating and throughout gestation. At postnatal day (PN) 170, mice underwent an intraperitoneal glucose tolerance test and were culled at PN180 for biochemical analysis. Mice exposed to selenium deficiency in utero had reduced fasting blood glucose but increased postprandial blood glucose concentrations. Male offspring from selenium-deficient litters had increased plasma insulin levels in conjunction with reduced plasma thyroxine (tetraiodothyronine or T4) concentrations. Conversely, females exposed to selenium deficiency in utero exhibited increased plasma thyroxine levels with no change in plasma insulin. This study demonstrates the importance of adequate selenium intake around pregnancy for offspring metabolic health. Given the increasing prevalence of metabolic disease, this study highlights the need for appropriate micronutrient intake during pregnancy to ensure a healthy start to life. Full article

The first months of life are a special time for the health development and protection of infants. Breastfeeding is the natural and best way of feeding an infant, and positively influences their development and health. Breast milk provides the ideal balance of nutrients for the infant and contains countless bioactive ingredients such as immunoglobulins, hormones, oligosaccharides and others. Human milk oligosaccharides (HMOs) are a very important and interesting constituent of human milk, and are the third most abundant solid component after lactose and lipids. They are a structurally and biologically diverse group of complex indigestible sugars. This article will discuss the mechanisms of action of HMOs in infants, such as their anti-adhesive properties, properties modulating the immune system, and impact on bacterial flora development. Many health benefits result from consuming HMOs. They also may decrease the risk of infection by their interactions with viruses, bacteria or protozoa. The commercial use of HMOs in infant formula, future directions, and research on the use of HMOs as a therapy will be discussed. Full article

This study aimed to investigate the beneficial effects of seabuckthorn freeze-dried powder on high-fat diet-induced obesity and related lipid metabolism disorders, and further explored if this improvement is associated with gut microbiota. Results showed that seabuckthorn freeze-dried powder administration decreased body weight, Lee’s index, adipose tissue weight, liver weight, and serum lipid levels. Moreover, treatment with seabuckthorn freeze-dried powder effectively reduced fat accumulation by modulating the relative expression of genes involved in lipid metabolism through down-regulation of encoding lipogenic and store genes, including SREBP-1c, PPAR-γ, ACC, and SCD1, and up-regulation of regulating genes of fatty acid oxidation, including HSL, CPT-1, and ACOX. Especially, seabuckthorn freeze-dried powder regulated the composition of gut microbiota, such as increasing the ratio of Firmicutes/Bacteroidetes, decreasing relative abundance of harmful bacteria (Desulfovibrio), and increasing relative abundance of beneficial bacteria (Akkermansia and Bacteroides). The changes of beneficial bacteria had a positive correlation with genes encoding lipolysis and a negative correlation with genes encoding lipid lipogenesis and store. The harmful bacteria were just the opposite. Besides, changes in gut microbiota had an obvious effect in the secretion of main metabolites—short-chain fatty acids (SCFAs), especially propionic acid. Thus, our results indicated that the seabuckthorn freeze-dried powder could ameliorate high-fat diet-induced obesity and obesity-associated lipid metabolism disorders by changing the composition and structure of gut microbiota. Full article

Enhanced Recovery after Surgery (ERAS) with sole carbohydrate (CHO) loading and postoperative early oral feeding (POEOF) shortened the length of postoperative (PO) hospital stays (LPOHS) without increasing complications. This study aimed to examine the impact of ERAS with preoperative whey protein-infused CHO loading and POEOF among surgical gynecologic cancer (GC) patients. There were 62 subjects in the intervention group (CHO-P), which received preoperative whey protein-infused CHO loading and POEOF; and 56 subjects formed the control group (CO), which was given usual care. The mean age was 49.5 ± 12.2 years (CHO-P) and 51.2 ± 11.9 years (CO). The trial found significant positive results which included shorter LPOHS (78.13 ± 33.05 vs. 99.49 ± 22.54 h); a lower readmission rate within one month PO (6% vs. 16%); lower weight loss (−0.3 ± 2.3 kg vs. −2.1 ± 2.3 kg); a lower C-reactive protein–albumin ratio (0.3 ± 1.2 vs. 1.1 ± 2.6); preserved muscle mass (0.4 ± 1.7 kg vs. −0.7 ± 2.6 kg); and better handgrip strength (0.6 ± 4.3 kg vs. −1.9 ± 4.7 kg) among CHO-P as compared with CO. However, there was no significant difference in mid-upper arm circumference and serum albumin level upon discharge. ERAS with preoperative whey protein-infused CHO loading and POEOF assured better PO outcomes. Full article

Ionized Mg (iMg) is considered the biologically active fraction of circulating total Mg (tMg). It is possible that iMg may be a more physiologically relevant marker than tMg. Using data from a double-blind pilot randomized controlled trial, we tested (1) whether oral Mg supplementation will increase iMg concentrations compared with placebo and (2) the relationship between iMg and tMg at baseline. Additionally, we evaluated the agreement between iMg measured in fresh whole blood versus stored samples. A total of fifty-nine participants were randomized 1:1 to oral Mg supplementation (400 mg/day, Mg Oxide) or placebo for 10 weeks. Fasting blood samples were obtained at baseline and follow-up. The analysis used linear regression and an intent-to-treat approach. Participants were generally healthy, the mean age was 62, and 73% were female. The baseline iMg and tMg were modestly and positively associated (r = 0.50). The ratio of baseline iMg to tMg was 64%. The mean supplement effect on iMg was 0.03 mmol/L (95% CI:0.01, 0.05) for Mg supplementation versus placebo. The supplement effect on iMg was not statistically significantly different according to baseline iMg status (above/below median). Compared to fresh blood, iMg was consistently higher in refrigerated and frozen samples by 0.14 and 0.20 mmol/L, respectively. In this relatively healthy adult population, Mg supplementation over 10 weeks resulted in increased iMg concentrations. Whether iMg is a more appropriate measure of Mg status than tMg, and the public health or clinical utility of measuring iMg remains to be determined. Full article

The pursuit of cholesterol lowering natural products with less side effects is needed for controlling dyslipidemia and reducing the increasing toll of cardiovascular diseases that are associated with morbidity and mortality worldwide. The present study aimed at the examining effects of p-methoxycinnamic acid diesters (PCO-C) from carnauba (Copernicia prunifera)-derived wax on cytotoxic, genotoxic responses in vitro and on dyslipidemia and liver oxidative stress in vivo, utilizing high-fat diet (HFD) chronically fed Swiss mice. In addition, we evaluated the effect of PCO-C on the expression of key cholesterol metabolism-related genes, as well as the structural interactions between PCO-C and lecithin-cholesterol acyl transferase (LCAT) in silico. Oral treatment with PCO-C was able to reduce total serum cholesterol and low-density lipoprotein (LDL) levels following HFD. In addition, PCO-C reduced excessive weight gain and lipid peroxidation, and increased the gene expression of LCAT following HFD. Furthermore, the high affinity of the studied compound (ΔG: −8.78 Kcal/mol) towards the active sites of mutant LCAT owing to hydrophobic and van der Waals interactions was confirmed using bioinformatics. PCO-C showed no evidence of renal and hepatic toxicity, unlike simvastatin, that elevated aspartate aminotransferase (AST) levels, a marker of liver dysfunction. Finally, PCO-C showed no cytotoxicity or genotoxicity towards human peripheral blood lymphocytes in vitro. Our results suggest that PCO-C exerts hypocholesterolemic effects. The safety of PCO-C in the toxicological tests performed and the reports of its beneficial biological effects render this a promising compound for the development of new cholesterol-lowering therapeutics to control dyslipidemia. More work is needed for further elucidating PCO-C role on lipid metabolism to support future clinical studies. Full article

Amino acids are components of proteins that also exist free-form in the body; their functions can be divided into (1) nutritional, (2) sensory, and (3) biological regulatory roles. The skeletal muscle, which is the largest organ in the human body, representing ~40% of the total body weight, plays important roles in exercise, energy expenditure, and glucose/amino acid usage—processes that are modulated by various amino acids and their metabolites. In this review, we address the metabolism and function of amino acids in the skeletal muscle. The expression of PGC1α, a transcriptional coactivator, is increased in the skeletal muscle during exercise. PGC1α activates branched-chain amino acid (BCAA) metabolism and is used for energy in the tricarboxylic acid (TCA) cycle. Leucine, a BCAA, and its metabolite, β-hydroxy-β-methylbutyrate (HMB), both activate mammalian target of rapamycin complex 1 (mTORC1) and increase protein synthesis, but the mechanisms of activation appear to be different. The metabolite of valine (another BCAA), β-aminoisobutyric acid (BAIBA), is increased by exercise, is secreted by the skeletal muscle, and acts on other tissues, such as white adipose tissue, to increase energy expenditure. In addition, several amino acid-related molecules reportedly activate skeletal muscle function. Oral 5-aminolevulinic acid (ALA) supplementation can protect against mild hyperglycemia and help prevent type 2 diabetes. β-alanine levels are decreased in the skeletal muscles of aged mice. β-alanine supplementation increased the physical performance and improved the executive function induced by endurance exercise in middle-aged individuals. Further studies focusing on the effects of amino acids and their metabolites on skeletal muscle function will provide data essential for the production of food supplements for older adults, athletes, and individuals with metabolic diseases. Full article

Background: To measure daily sodium intake in patients on chronic hemodialysis and to compare the intake of nutrients, minerals, trace elements, and vitamins in patients who had a daily sodium intake below or above the value of 1500 mg recommended by the American Heart Association. Methods: Dietary intake was recorded for 3 days by means of 3-day diet diaries in prevalent patients on chronic hemodialysis. Each patient was instructed by a dietitian on how to fill the diary, which was subsequently signed by a next of kin. Results: We studied 127 patients. Mean sodium intake (mg) was 1295.9 ± 812.3. Eighty-seven (68.5%) patients had a daily sodium intake <1500 mg (group 1) and 40 (31.5%) ≥ 1500 mg (group 2). Correlation between daily sodium intake and daily calorie intake was significant (r = 0.474 [0.327 to 0.599]; p < 0.0001). Daily calorie intake (kcal/kg/day) was lower in group 1 (21.1 ± 6.6; p = 0.0001) than in group 2 (27.1 ± 10.4). Correlation between daily sodium intake and daily protein intake was significant (r = 0.530 [0.392 to 0.644]; p < 0.0001). The daily protein intake (grams/kg/day) was lower in group 1 (0.823 ± 0.275; p = 0.0003) than in group 2 (1.061 ± 0.419). Daily intake of magnesium, copper, iron, zinc, and selenium was significantly lower in group 1 than in group 2. Daily intake of vitamin A, B2, B3, and C did not differ significantly between group 1 and group 2. Daily intake of vitamin B1 was significantly lower in group 1 than in group 2. Significantly lower was, in group 1 than in group 2, the percentage of patients within the target value with regard to intake of calories (11.5% vs. 37.5%; p = 0.001) and proteins (9.2% vs. 27.5%; p = 0.015) as well as of iron (23% vs. 45%; p = 0.020), zinc (13.8% vs. 53.8%; p = 0.008) and vitamin B1 (8.1% vs. 50%; p < 0.001). Conclusion: A low daily intake of sodium is associated with an inadequately low intake of calorie, proteins, minerals, trace elements, and vitamin B1. Nutritional counselling aimed to reduce the intake of sodium in patients on chronic hemodialysis should not disregard an adequate intake of macro- and micronutrients, otherwise the risk of malnutrition is high. Full article

Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials. Full article

Early introduction of complementary foods can have a detrimental impact on children’s long-term health. This study examined the timing and determinants of early introduction of core and discretionary foods among infants in Sydney, Australia. Mothers (n = 1035) from an ongoing population-based birth cohort study were interviewed at 8, 17, 34 and 52 weeks postpartum. The outcome was ‘age at which particular core and discretionary food items were first introduced’. Multivariable logistic regression models were used to investigate family and infant-related determinants of early introduction of core (<17 weeks of age) and discretionary foods (<52 weeks of age). Of the 934 mother-infant dyads interviewed, 12% (n = 113) of infants were introduced core foods before 17 weeks of age (median: 22). Mothers working part-time (adjusted odds ratio (OR): 3.42, 95% confidence interval (CI): 1.54–7.62) and those exclusively formula-feeding their babies at four-weeks postpartum (adjusted OR 3.26, 95% CI: 1.99–5.33) were most likely to introduce core foods early. Ninety-five percent (n = 858) of infants were introduced discretionary foods before 52 weeks of age (median: 28). Low socio-economic status was significantly associated with early introduction of discretionary foods (adjusted OR: 3.72, 95% CI: 1.17–11.78). Compliance with infant feeding guidelines related to core foods was better; however, discretionary foods were introduced early in most infants. Full article

Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many cancers. Phytoestrogens’ structural resemblance to 17 β-estradiol allows their binding to ERβ isoform predominantly, and therefore, expression of genes connected with elevated proliferation, motility and invasiveness of cancer cells may be downregulated. Among polyphenolic compounds with phytoestrogenic activity, there are isoflavones from Trifolium pratense L. (red clover) sprouts, containing high amounts of formononetin and biochanin A and their glycosides. To determine the source of the most biologically active isoflavones, we obtained four extracts from sprouts before and after their lactic fermentation and/or β-glucosidase treatment. Our previous results of ITC (isothermal titration calorimetry) modelling and a docking simulation showed clover isoflavones’ affinity to ERβ binding, which may downregulate cancer cell proliferation and migration. Thus, the biological activity of T. pratense sprouts’ extracts was checked under in vitro conditions against highly invasive human breast cancer cell line MDA-MB-231 and non-invasive human breast cancer cell line MCF-7 cells. To compare extracts’ activities acquired for cancer cells with those activities against normal cells, as a third model we choose human umbilical vein endothelial cells (HUVEC), which, due to their migration abilities, are involved in blood vessel formation. Extracts obtained from fermented sprouts at IC₀ dosages were able to inhibit migration of breast cancer cells through their influence on intracellular ROS generation; membrane stiffening; adhesion; regulation of MMP-9, N-cadherin and E-cadherin at transcriptional level; or VEGF secretion. Simultaneously, isolated phenolics revealed no toxicity against normal HUVEC cells. In the manuscript, we proposed a preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones. In this manner, T. pratense sprouts, especially after their lactic fermentation, can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties. Full article

The oral processing of food is important for eating and digestion in order to gain energy and nutrients. Due to disease, injury, or aging, individuals may experience difficulties in this process. These difficulties often lead to dysphagia, which is associated with malnutrition. Thus, it is of importance to find solutions and strategies to enable food intake. It is well known that sour and/or carbonated foods and drinks increase saliva secretion and trigger the swallowing reflex. However, knowledge regarding how subsequent food intake is impacted is lacking. The aim of this study was to clarify whether sour and/or carbonated foods and drinks had subsequent impacts on swallowing function. Twelve healthy participants evaluated eleven foods and drinks in terms of their ability to increase saliva production and ease the swallowing of subsequent food. Results showed that sourness and carbonation had positive impacts on saliva secretion and swallowing. No correlation was found between the pH/sourness of the foods and the ease of swallowing them. It was concluded that the ingestion of cherry tomatoes, natural yoghurt, and, in particular, citrus juice made swallowing of a neutral cracker easier. These results may be used to increase food intake among dysphagia patients. Full article

Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on postprandial lipid metabolism and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with healthy blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol (p = 0.042) and apolipoprotein (Apo)B-100 (p = 0.003) levels, and decreased postprandial maximum concentrations (C_max) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels (p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites. This study suggests that LPQ180 might be developed as a functional ingredient to help maintain healthy postprandial lipid levels through modulating gut environment. Full article

Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this exploratory pilot study was to initiate the evaluation of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38 ± 15 years/age and 7 females at 34 ± 18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 g of EAAS twice/day (BID)) or high dose (HD: 13 g of EAAS BID). Five of the twenty-five enrolled participants dropped out of the intervention. Both groups consumed the supplement BID for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual-energy X-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at p < 0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p = 0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407 ± 141 ng/mL and HD at 429 ± 196 ng/mL, indicating chronic and excess alcohol consumption. The HD of the proprietary EAAS formulation consumed BID seemed to lower IHL in individuals with mild to moderate AUD. We suggest that further studies in a larger cohort be conducted to more completely address this important area of investigation. Full article

Stunting in children less than five years of age is widespread in Sub-Saharan Africa. We aimed to: (i) evaluate how the prevalence of stunting has changed by socio-economic status and rural/urban residence, and (ii) assess inequalities in children’s diet quality and access to maternal and child health care. We used data from nationally representative demographic and health- and multiple indicator cluster-surveys (DHS and MICS) to disaggregate the stunting prevalence by wealth quintile and rural/urban residence. The composite coverage index (CCI) reflecting weighed coverage of eight preventive and curative Reproductive, Maternal, Neonatal, and Child Health (RMNCH) interventions was used as a proxy for access to health care, and Minimum Dietary Diversity Score (MDDS) was used as a proxy for child diet quality. Stunting significantly decreased over the past decade, and reductions were faster for the most disadvantaged groups (rural and poorest wealth quintile), but in only 50% of the countries studied. Progress in reducing stunting has not been accompanied by improved equity as inequalities in MDDS (p < 0.01) and CCI (p < 0.001) persist by wealth quintile and rural-urban residence. Aligning food- and health-systems’ interventions is needed to accelerate stunting reduction more equitably. Full article

Animal source foods (ASF) provide nutrients essential to child growth and development yet remain infrequently consumed in rural Nepal. Agriculture and nutrition programs aim to increase ASF intake among children through small-scale animal husbandry projects. The relationship between livestock ownership and children’s consumption of ASF, however, is not well established. This study examined associations between livestock ownership and the frequency with which Nepali children consume eggs, dairy, and meat. We analyzed longitudinal 7-day food frequency data from sentinel surveillance sites of the Policy and Science of Health, Agriculture and Nutrition (PoSHAN) study. Data consisted of surveys from 485 Nepali farming households conducted twice per year for two years (a total of 1449 surveys). We used negative binomial regression analysis to examine the association between the number of cattle, poultry, and meat animals (small livestock) owned and children’s weekly dairy, egg, and meat intakes, respectively, adjusting for household expenditure on each food type, mother’s education level, caste/ethnicity, agroecological region, season, and child age and sex. We calculated predicted marginal values based on model estimates. Children consumed dairy 1.4 (95% CI 1.1–2.0), 2.3 (1.7–3.0) and 3.0 (2.1–4.2) more times per week in households owning 1, 2–4 and >4 cattle, respectively, compared to children in households without cattle. Children consumed eggs 2.8 (2.1–3.7) more times per week in households owning 1 or 2 chickens compared to children in households without chickens. Child intake of meat was higher only in households owning more than seven meat animals. Children’s intakes of dairy, eggs, and meat rose with household expenditure on these foods. Small-scale animal production may be an effective strategy for increasing children’s consumption of eggs and dairy, but not meat. Increasing household ability to access ASF via purchasing appears to be an important approach for raising children’s intakes of all three food types. Full article

AceDoPC^® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC^® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of ¹³C-labeled DHA after oral intake of a single dose of ¹³C-AceDoPC^®, in comparison with ¹³C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the ¹³C enrichment of DHA-containing lipids. ¹³C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC^® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, ¹³C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the ¹³C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC^® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC^® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion. Full article

Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions. Full article

Morinda citrifolia, a fruit generally known as “Noni”, has been traditionally used in parts of East Asia to relieve inflammatory diseases. Although several studies using noni have been reported, the effect of fermented Morinda citrifolia (F.NONI) on atopic dermatitis (AD) has not been investigated. Thus, we aimed to investigate the improving effect of F.NONI treatment on AD-like skin lesions and elucidate molecular mechanisms. F.NONI was prepared by the fermentation of noni fruit with probiotics and then extracted. F.NONI was orally administrated to NC/Nga mice to evaluate its therapeutic effect on 2,4-dinitrochlorobenzene (DNCB)-induced AD. Oral administration of F.NONI significantly alleviated AD lesions and symptoms such as dermatitis scores, ear thickness, scratching behavior, epidermal thickness, and infiltration of inflammatory cells (e.g., mast cells and eosinophils). In addition, F.NONI treatment reduced the levels of histamine, IgE and IgG1/IgG2a ratio, thymus and activation regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) in serum and beneficially modulated the expressions of Th1, Th2, Th17, and Th22-mediated cytokines in lesioned skin and splenocytes. Furthermore, the expressions of the skin barrier-related proteins including filaggrin (FLG), loricrin (LOR), involucrin (IVL), zonula occludens-1 (ZO-1), and occludin (OCC) were restored by F.NONI treatment. Taken together, these results suggest that F.NONI could be a therapeutic agent to attenuate AD-like skin lesions through modulating the immune balance and skin barrier function. Full article

Docosahexaenoic acid (DHA) is an essential component for brain and visual acuity development during foetal and early postnatal life. A newly released directive under the European Commission stipulates DHA as a mandatory ingredient in infant formula. This poses challenges to manufacturers in preserving the stability and bioavailability of DHA at levels akin to human breast milk. The aims of this study were (a) to investigate the bioavailability of microencapsulated omega-3 DHA formulations in healthy toddlers compared with high DHA fish oil for a one-month period and (b) to assess the effect of DHA supplementation on children’s sleep and cry patterns. Sixty toddlers were randomly allocated to four groups: 1. unfortified formula, 2. unfortified formula plus high DHA tuna oil, 3. fortified formula with dairy-based microencapsulated high DHA tuna oil powder, and 4. fortified formula with allergenic-free microencapsulated high DHA tuna oil powder. Bioavailability was assessed from both blood and faecal fatty acid levels. The results showed an enhanced bioavailability with significantly greater concentrations of blood DHA levels in formulas with microencapsulated powders. There were no significant effects of treatment on sleep and cry patterns. Application and delivery of microencapsulated DHA tuna oil powder in toddlers’ formula provided better bioavailability of the active DHA. Full article

The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented; however, there are potential risks of exceeding the upper tolerable limit, particularly in vulnerable populations. We conducted a population-based analysis of the Food Fortification Initiative dataset to determine the strength of the evidence regarding reports of decreased NTDs at the national level in response to mandatory folic acid fortification of cereal grains. We found a very weak correlation between NTD prevalence and the level of folic acid fortification, irrespective of the cereal grain fortified (wheat, maize or rice). Stratification of the data based on socioeconomic status (SES) indicated a strong linear relationship between reduced NTDs and better SES. We conclude that national fortification with folic acid is not associated with a significant decrease in the prevalence of NTDs at the population level. Full article

Ginsenosides have been reported to possess various pharmacological effects, including anticancer effects. Nevertheless, there are few reports about the antitumor activity and mechanisms of ginsenoside Rg5 against breast cancer cells. In the present study, the major ginsenoside Rb1 was transformed into the rare ginsenoside Rg5 through enzymatic bioconversion and successive acid-assisted high temperature and pressure processing. Ginsenosides Rb1, Rg3, and Rg5 were investigated for their antitumor effects against five human cancer cell lines via the MTT assay. Among them, Rg5 exhibited the greatest cytotoxicity against breast cancer. Moreover, Rg5 remarkably suppressed breast cancer cell proliferation through mitochondria-mediated apoptosis and autophagic cell death. LC3B-GFP/Lysotracker and mRFP-EGFP-LC3B were utilized to show that Rg5 induced autophagosome-lysosome fusion. Western blot assays further illustrated that Rg5 decreased the phosphorylation levels of PI3K, Akt, mTOR, and Bad and suppressed the PI3K/Akt signaling pathway in breast cancer. Moreover, Rg5-induced apoptosis and autophagy could be dramatically strengthened by the PI3K/Akt inhibitor LY294002. Finally, a molecular docking study demonstrated that Rg5 could bind to the active pocket of PI3K. Collectively, our results revealed that Rg5 could be a potential therapeutic agent for breast cancer treatment. Full article

Human milk is rich in nutritional factors, such as alpha-lactalbumin (α-Lac), and important for neonatal development, but nutrient supplementation may be required for optimal growth. Using a pig model, we hypothesized that α-Lac-enriched whey protein concentrate (WPC) supplementation improves neonatal development. Cesarean-delivered preterm pigs were fed either dilute bovine milk (REF) or REF milk supplemented with WPC with normal (STANDARD-ALPHA) or high (HIGH-ALPHA) α-Lac. Clinical, gut, immune and cognitive endpoints (open field, T-maze) were assessed and tissues collected at Day 19. The growth of STANDARD-ALPHA and HIGH-ALPHA were higher than REF (31 vs. 19 g/kg/d). Most organ weights, gut, immunity and brain variables were similar between WPC groups. HIGH-ALPHA had a higher bone mineral content, colon microbial diversity and an abundance of specific bacteria and microbial metabolites, and tended to show a faster food transit time (p = 0.07). Relative to REF, WPC pigs showed higher relative organ weights, blood amino acids, blood neutrophil function, and microbial metabolites, but lower brush-border enzyme activities and plasma cortisol. Cognition outcomes did not differ among the groups. In conclusion, WPC supplementation of milk improved some growth, gut and immunity parameters in preterm pigs. However, increasing the α-Lac content beyond human milk levels had limited effects on the immature gut and developing brain. Full article

The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess the impact of a 6-week non-energy-restricted KD on the abdominal fat distribution and the hepatic fat composition in healthy adults. Body fat distribution and composition were measured by comparing magnetic resonance imaging (MRI) and spectroscopy (MRS) results with air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) measurements. A total of 12 subjects from the KetoPerformance study were recruited for this ancillary study. Body mass index (BMI), total mass, total fat mass, total subcutaneous mass, and subcutaneous fat mass decreased significantly. None of the MRS parameters showed a significant change during the study. Even though the average change in body weight was >2kg, no significant changes in intrahepatic lipid (IHL) content could be observed. Total fat mass and total fat-free mass derived from MRI has a strong correlation with the corresponding values derived from BIA and ADP data. BMI and the absolute fat parameter of all three modalities decreased, but there were no or only minor changes regarding the fat-free parameter. Magnetic resonance imaging provides body composition information on abdominal fat distribution changes during a ketogenic diet. This information is complementary to anthropomorphic and laboratory measures and is more detailed than the information provided by ADP and BIA measures. It was shown that there was no significant change in internal fat distribution, but there was a decrease in subcutaneous fat. Full article