Nutrients, Volume 13, Issue 5 (May 2021) – 352 articles

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials. Full article

Resveratrol and its 2-methoxy derivative pterostilbene are two phenolic compounds that occur in foodstuffs and feature hepato-protective effects. This study is devoted to analysing and comparing the metabolic effects of pterostilbene and resveratrol on gut microbiota composition in rats displaying NAFLD induced by a diet rich in saturated fat and fructose. The associations among changes induced by both phenolic compounds in liver status and those induced in gut microbiota composition were also analysed. For this purpose, fifty Wistar rats were distributed in five experimental groups: a group of animals fed a standard diet (CC group) and four additional groups fed a high-fat high-fructose diet alone (HFHF group) or supplemented with 15 or 30 mg/kg bw/d of pterostilbene (PT15 and PT30 groups, respectively) or 30 mg/kg bw/d of resveratrol (RSV30 group). The dramatic changes induced by high-fat high-fructose feeding in the gut microbiota were poorly ameliorated by pterostilbene or resveratrol. These results suggest that the specific changes in microbiota composition induced by pterostilbene (increased abundances of Akkermansia and Erysipelatoclostridium, and lowered abundance of Clostridum sensu stricto 1) may not entirely explain the putative preventive effects on steatohepatitis. Full article

Fasting and postprandial hypertriglyceridemia are causal risk factors for atherosclerosis. The prevalence of hypertriglyceridemia is approximately 25–30% and most hypertriglyceridemic patients suffer from mild to moderate hypertriglyceridemia. Data regarding dietary interventions on postprandial triglyceride metabolism of mildly to moderately hypertriglyceridemic patients is, however, sparse. In a randomized controlled trial, eight mildly hypertriglyceridemic patients and five healthy, normolipidemic controls received three separate standardized fat-meals containing either saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), or medium-chain fatty acids (MCFA) in a randomized order. Fasting and postprandial lipid parameters were determined over a 10 h period and the (incremental) area under the curve (AUC/iAUC) for plasma triglycerides and other parameters were determined. MCFA do not lead to a significant elevation of postprandial total plasma triglycerides and other triglyceride parameters, while both SFA (patients: p = 0.003, controls: p = 0.03 compared to MCFA) and MUFA (patients: p = 0.001; controls: p = 0.14 compared to MCFA) do lead to such an increase. Patients experienced a significantly more pronounced increase of plasma triglycerides than controls (SFA: patients iAUC = 1006 mg*h/dL, controls iAUC = 247 mg*h/dL, p = 0.02; MUFA: patients iAUC = 962 mg*h/dL, controls iAUC = 248 mg*h/dL, p = 0.05). Replacing SFA with MCFA may be a treatment option for mildly to moderately hypertriglyceridemic patients as it prevents postprandial hypertriglyceridemia. Full article

There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09; 95%CI: 1.23–3.55, I² = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49; 95%CI: 1.11–1.99, I² = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men. Full article

The effects of exercise on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training increases the expression of molecules involved in carbohydrate digestion and absorption. Exercise was also shown to increase the blood concentration of glucagon-like peptide-2 (GLP-2), which regulates carbohydrate digestion and absorption in the small intestine. Therefore, we investigated the effects of exercise on the expression of molecules involved in intestinal digestion and absorption, including GLP-2. Six-week-old male mice were divided into a sedentary (SED) and low-intensity exercise (LEx) group. LEx mice were required to run on a treadmill (12.5 m/min, 1 h), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest, and plasma, jejunum, ileum, and colon samples were collected, followed by analysis via IHC, EIA, and immunoblotting. The levels of plasma GLP-2 and the jejunum expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter 2 (GLUT2) were higher in LEx mice. Thus, we showed that acute low-intensity exercise affects the expression of molecules involved in intestinal carbohydrate digestion and absorption via GLP-2. Our results suggest that exercise might be beneficial for small intestine function in individuals with intestinal frailty. Full article

Background: Hybrid nutrient density scores are based on both nutrients and selected food groups. Objective: To compare the new hybrid nutrient-rich food NRFh 4:3:3 score to other nutrient-rich food (NRF) scores, energy density, and energy cost and to model the impact on the Healthy Eating Index (HEI-2015) of partially replacing less nutrient-rich with more nutrient-rich foods. Methods: Analyses were based on 5870 foods and beverages in the Food and Nutrient Database for Dietary Studies and on 24 h dietary recalls from the National Health and Nutrition Examination Survey (NHANES 2013–16). The NRFh 4:3:3 model was based on four nutrients to encourage (protein fiber, potassium, MUFA + PUFA); three food groups to encourage (dairy, fruit, whole grains); and three nutrients to limit (saturated fat, added sugar, sodium). Ratings generated by NRFh 4:3:3 and by other NRF models were correlated with score components, energy density (kcal/100 g), and energy cost (USD/100 kcal). The impact on HEI-2015 of replacing foods in the lowest nutrient density tertile (T1) with top tertile (T3) foods at 10%, 20%, 30%, and 100% equicaloric replacement was modeled using NHANES 2013–16 dietary data by population subgroups. Results: The NRFh 4:3:3 model awarded higher scores to foods containing dairy, fruit, and whole grains and proportionately lower scores to vegetables when compared to the NRF 9.3 model. Higher NRF and NRFh nutrient density scores were linked to lower energy density and higher energy cost; however, both correlations were lower for the NRFh 4:3:3. Isocaloric replacement of bottom tertile with top tertile foods as rated by both models led to significantly higher HEI-2105 values, based on complete (100%) and on partial (10–30%) replacement. Conclusion: The new NRFh 4:3:3 model provides the basis for developing new metrics of affordable nutrient density. The model identified “best value” food categories that were both affordable and nutrient-rich. Total and partial replacement of low nutrient density with high nutrient density foods was associated with higher HEI-2015 scores, suggesting that even partial inclusion of more nutrient dense foods in the diet may have an important impact on total diet quality. Full article

Little is known about nutritional factors during weight loss on digital commercial weight loss programs. We examined how nutritional factors relate to weight loss for individuals after 4 and 18 months on a mobile commercial program with a food categorization system based on energy density (Noom). This is a two-part (retrospective and cross-sectional) cohort study. Two time points were used for analysis: 4 months and 18 months. For 4-month analyses, current Noom users who met inclusion criteria (n = 9880) were split into 5% or more body weight loss and stable weight loss (0 ± 1%) groups. Individuals who fell into one of these groups were analyzed at 4 months (n = 3261). For 18-month analyses, individuals from 4-month analyses who were still on Noom 18 months later were invited to take a one-time survey (n = 803). At 18 months 148 participants were analyzed. Noom has a system categorizing foods as low-, medium-, and high-energy-dense. Measures were self-reported proportions of low-, medium-, and high-energy-dense foods, and self-reported nutritional factors (fruit and vegetable intake, dietary quality, nutrition knowledge, and food choice). Nutritional factors were derived from validated survey measures, and food choice from a novel validated computerized task in which participants chose a food they would want to eat right now. ANOVAs compared participants with 5% or more body weight loss and participants with stable weight (0 ± 1%) at 4 months on energy density proportions. Analyses at 18 months compared nutritional factors across participants with >10% (high weight loss), 5–10% (moderate weight loss), and less than 5% body weight loss (low weight loss), and then assessed associations between nutritional factors and weight loss. Individuals with greater weight loss reported consuming higher proportions of low-energy-dense foods and lower proportions of high-energy-dense foods than individuals with less weight loss at 4 months and 18 months (all ps < 0.02). Individuals with greater weight loss had higher fruit and vegetable intake (p = 0.03), dietary quality (p = 0.02), nutrition knowledge (p < 0.001), and healthier food choice (p = 0.003) at 18 months. Only nutrition knowledge and food choice were associated with weight loss at 18 months (B = −19.44, 95% CI: −33.19 to −5.69, p = 0.006; B = −5.49, 95% CI: −8.87 to −2.11, p = 0.002, respectively). Our results highlight the potential influence of nutrition knowledge and food choice in weight loss on a self-managed commercial program. We also found for the first time that in-the-moment inclination towards food even when just depicted is associated with long-term weight loss. Full article

Accumulated lipid droplets in liver cause nonalcoholic fatty liver disease (NAFLD). Deep ocean water (DOW) containing high levels of magnesium, calcium, and potassium, etc. was proven to suppress hepatic lipid in obese rats fed high fat diet in the previous study. However, the effect of mineral compositions of DOW on the prevention of NAFLD is still unclear. This study removed calcium and potassium from DOW for modulating the mineral composition, and further compared the effects of DOW (D1(Mg + Ca + K)), DOW with low potassium (D2(Mg + Ca)), and DOW with low calcium and potassium (D3(Mg)) on the prevention of NAFLD in the mice model fed with high fat diet. In these results, DOW with high magnesium levels reduced serum and liver triglyceride and cholesterol levels and serum AST and ALT activities. However, when the calcium and/or potassium minerals were removed from DOW, the effects of reduction of triglyceride level, inhibition of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor-alpha (PPAR-α) expressions, and activation of superoxide dismutase, catalase, and glutathione reductase activities would be weaker. In conclusion, DOW including magnesium, calcium and potassium minerals has the strongest preventive effect on NAFLD in a mouse model by increasing the antioxidant system and inhibiting fatty acid biosynthesis. Full article

This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines’ level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals. Full article

Dietary habits are of considerable interest as a modifiable factor for the maintenance of muscle health, especially sarcopenia. The present study aimed to investigate the association between dietary intake and sarcopenia prevalence in community-dwelling Japanese subjects. This cross-sectional study was conducted using data from the fifth survey of the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) study, and 1345 participants (437 men and 908 women) aged ≥60 years were included in the analysis. Sarcopenia was determined by the definition of the Asian Working Group for Sarcopenia established in 2014, and dietary intake was assessed with the brief-type self-administered diet history questionnaire. Overall, 77 subjects (5.7%) were identified as having sarcopenia, 5.0% of men and 6.1% of women. Multiple logistic regression analysis showed that the odds ratios of sarcopenia for the dietary intake of vitamin E (α-tocopherol, 0.14 (CI 0.04–0.49), β-tocopherol (0.24, CI 0.07–0.78), γ-tocopherol (0.28, CI 0.09–0.87), and fats (fat 0.27, CI 0.08–0.96; monounsaturated fatty acids, 0.22, CI 0.07–0.72, polyunsaturated fatty acids, 0.28, CI 0.09–0.89) at the highest quantile were significantly lower compared with those at the lowest quantile. Therefore, higher dietary intakes of vitamin E and fats would be associated with a lower prevalence of sarcopenia. Full article

The study aim was to test hypotheses informed by self-determination theory (SDT) regarding associations of adolescent motivators for weight loss and family feeding practices on understanding adolescent weight management and dietary behaviors. Adolescents (n = 71) with obesity were recruited from a large medical center in the Midwest USA and completed questionnaire assessments via an online survey. Results supported hypotheses that endorsement of health motivators for weight loss, conceptualized as autonomous (intrinsic) motivation, and positive family support would be associated with healthier weight management practices and dietary behaviors. Nuanced findings related to social- and self-esteem-related motivators for weight loss indicated a need for further understanding of these weight-loss motivators in the context of SDT. The current study findings highlight the importance of addressing motivational factors and family influences in research and practice related to promoting healthy dietary habits and weight management strategies among adolescents with obesity. Full article

The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota–gut–brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants. Full article

Common mental disorders (CMD) are characterized by non-psychotic depressive symptoms, anxiety and somatic complaints, which affect the performance of daily activities. This study aimed to analyze prevalence of diet quality among adults with and without CMD from 2006 to 2017, to study the frequency of food consumption and diet quality according to mental status and age, and to determine which sociodemographic, lifestyle and health-related factors are associated with poor/moderate diet quality, according to mental status. A nationwide cross-sectional study was performed in adults with (n = 12,545) and without CMD (n = 48,079). The data were obtained from three Spanish National Health Surveys (2006, 2011/2012 and 2017). Two logistic regression analyses were used to identify factors associated with diet quality in people with and without CMD. Among those with CMD, the probability of having poor/moderate diet quality was significantly lower for overweight or obese people and those who took part in leisure-time physical activity. Among those without CMD, university graduates were less likely to have a poor/moderate diet quality. Good diet quality was observed more in older adults (≥65 years old) than in emerging (18–24 years old) or young adults (25–44 years old), regardless of mental status. Full article

Necrotizing enterocolitis (NEC), which is characterized by severe intestinal inflammation and in advanced stages necrosis, is a gastrointestinal emergency in the neonate with high mortality and morbidity. Despite advancing medical care, effective prevention strategies remain sparse. Factors contributing to the complex pathogenesis of NEC include immaturity of the intestinal immune defense, barrier function, motility and local circulatory regulation and abnormal microbial colonization. Interestingly, enteral feeding is regarded as an important modifiable factor influencing NEC pathogenesis. Moreover, breast milk, which forms the currently most effective prevention strategy, contains many bioactive components that are known to support neonatal immune development and promote healthy gut colonization. This systematic review describes the effect of different enteral feeding interventions on the prevention of NEC incidence and severity and the effect on pathophysiological mechanisms of NEC, in both experimental NEC models and clinical NEC. Besides, pathophysiological mechanisms involved in human NEC development are briefly described to give context for the findings of altered pathophysiological mechanisms of NEC by enteral feeding interventions. Full article

Suggestions that a food contains healthy ingredients or that it can provide beneficial effects upon consumption have been regulated in the EU since 2006. This paper describes the analysis of how this nutrition and health claim regulation has resulted in over 300 authorised claims and how the authorisation requirements and processes have affected the use of claims on foods. Five challenges are identified that negatively affect the current legislation dealing with nutrition and health claims: non-reviewed botanical claims (as well as on hold claims for infants and young children), the lack of nutrient profiles and the focus of claims on single ingredients, consumer understanding, research into health effects of nutrition and finally, enforcement. These challenges are shown to influence the goals of the regulation: protecting consumers from false and misleading claims and stimulating the development of a level playing field in the EU, to foster innovation. Tackling these political and scientific substantiation questions for health claims, together with continuously analysing the understanding and usage of claims by consumers and operators will ensure that the NHCR will stay effective, today and in the future. Full article

Background: Most Australians do not meet vegetable intake recommendations. Vegetables are most often consumed in evening meals. However, they often require preparation and therefore cooking skills. Convenience cooking products such as meal bases/concentrates and ready-made sauces are increasingly common and popular and may help address the barriers to vegetable consumption in terms of cost and time. These products also typically provide recipes, which include vegetables, and as such, may help address the barriers of cooking skills, confidence, and creativity. However, the relationships between the use of these products, cooking confidence, and cooking creativity remain unknown. Methods: Australian adults were surveyed (snowball recruitment, n = 842) on their use of convenience cooking products (meal bases/recipe concentrates, simmer sauces, marinades, and other cooking sauces), cooking confidence (7 item scale) and creativity (6 item scale), and demographic information. Results: Overall, 63.2% of participants reported using convenience cooking products. Those using these products had lower mean cooking skills confidence and creativity scores than those who did not, in all product categories assessed. Among users, those who reported "always" following the recipes provided had lower mean cooking confidence and creativity scores than those who followed the recipes less regularly. Conclusions: Therefore, improving the vegetable content of recipes provided with these products may be a tool to increase vegetable intake by users with lower cooking skills (confidence and creativity). This may complement traditional approaches such as education in improving vegetable intake. Full article

Non-alcoholic steatohepatitis (NASH), one of the deleterious stages of non-alcoholic fatty liver disease, remains a significant cause of liver-related morbidity and mortality worldwide. In the current work, we used an exploratory data analysis to investigate time-dependent cellular and mitochondrial effects of different supra-physiological fatty acids (FA) overload strategies, in the presence or absence of fructose (F), on human hepatoma-derived HepG2 cells. We measured intracellular neutral lipid content and reactive oxygen species (ROS) levels, mitochondrial respiration and morphology, and caspases activity and cell death. FA-treatments induced a time-dependent increase in neutral lipid content, which was paralleled by an increase in ROS. Fructose, by itself, did not increase intracellular lipid content nor aggravated the effects of palmitic acid (PA) or free fatty acids mixture (FFA), although it led to an up-expression of hepatic fructokinase. Instead, F decreased mitochondrial phospholipid content, as well as OXPHOS subunits levels. Increased lipid accumulation and ROS in FA-treatments preceded mitochondrial dysfunction, comprising altered mitochondrial membrane potential (ΔΨm) and morphology, and decreased oxygen consumption rates, especially with PA. Consequently, supra-physiological PA alone or combined with F prompted the activation of caspase pathways leading to a time-dependent decrease in cell viability. Exploratory data analysis methods support this conclusion by clearly identifying the effects of FA treatments. In fact, unsupervised learning algorithms created homogeneous and cohesive clusters, with a clear separation between PA and FFA treated samples to identify a minimal subset of critical mitochondrial markers in order to attain a feasible model to predict cell death in NAFLD or for high throughput screening of possible therapeutic agents, with particular focus in measuring mitochondrial function. Full article

(1) Background: Several studies have reported associations between maternal diet in terms of single foods or nutrients and human milk compounds, while the overall role of maternal diet and related dietary patterns has rarely been investigated. (2) Methods: Between 2012 and 2014, we enrolled 300 healthy Italian mothers, who exclusively breastfed their infant. During a hospital visit at 6 weeks postpartum, a sample of freshly expressed foremilk was collected and information on maternal dietary habits in the postpartum period was obtained through an interviewer-administered food frequency questionnaire. We applied principal component factor analysis to selected nutrients in order to identify maternal dietary patterns, and assessed correlations in human milk macronutrients and fatty acids across levels of dietary patterns. (3) Results: Five dietary patterns were identified, named “Vitamins, minerals and fibre”, “Proteins and fatty acids with legs”, “Fatty acids with fins”, “Fatty acids with leaves”, “Starch and vegetable proteins”. These dietary patterns were correlated with some milk components, namely fatty acids, and in particular ω-3 and its subcomponents. (4) Conclusions: This study showed that overall maternal dietary habits during breastfeeding may influence human milk composition, suggesting the importance of adequate maternal nutrition during lactation not only for the mother herself but also to provide the infant with milk containing adequate amount and quality of nutrients for a balanced nutrition. Full article

The aim of this observational study was investigating the possible correlation between adherence to the Mediterranean diet (MeD) and SARS-COV-2 infection rates and severity among healthcare professionals (HCPs). An online self-administrated questionnaire (evaluating both MeD adherence and dietary habits) was filled out by HCPs working in Piedmont (Northern Italy) from 15 January to 28 February 2021. Out of the 1206 questionnaires collected, 900 were considered reliable and analyzed. Individuals who reported the SARS-COV-2 infection (n = 148) showed a significantly lower MeD score, with a lower adherence in fruit, vegetables, cereals, and olive oil consumption. In a logistic regression model, the risk of infection was inversely associated with the MeD score (OR = 0.88; 95% CI 0.81–0.97) and the consumption of cereals (OR = 0.64; 0.45–0.90). Asymptomatic individuals with SARS-COV-2 infection reported a lower intake of saturated fats than symptomatic; individuals requiring hospitalization were significantly older and reported worse dietary habits than both asymptomatic and symptomatic individuals. After combining all symptomatic individuals together, age (OR = 1.05; 1.01–1.09) and saturated fats intake (OR = 1.09; 1.01–1.17) were associated with the infection severity. HCPs who reported a SARS-COV-2 infection showed a significantly lower MeD score and cereal consumption. The infection severity was directly associated with higher age and saturated fat intake. Full article

The available data on the association between micronutrients in the blood and non-alcoholic fatty liver disease (NAFLD) are limited. To investigate the clinical implications of this relationship, we sought to identify the difference in the serum levels of vitamins A and E according to NAFLD status using data from the seventh Korea National Health and Nutrition Examination Survey. In this cross-sectional study of the Korean population, NAFLD and its severity were defined using prediction models. Differences in the prevalence and severity of NAFLD were analyzed according to serum retinol (vitamin A) and alpha (α)-tocopherol (vitamin E) levels. Serum levels of retinol and α-tocopherol were positively correlated with the prevalence of NAFLD. In most prediction models of the NAFLD subjects, serum retinol deficiency was significantly correlated with advanced fibrosis, while serum α-tocopherol levels did not differ between individuals with or without advanced fibrosis. Similar trends were also noted with cholesterol-adjusted levels of α-tocopherol. In summary, while circulating concentrations of retinol and α-tocopherol were positively associated with the presence of NAFLD, advanced liver fibrosis was only correlated with serum retinol levels. Our findings could provide insight into NAFLD patient care at a micronutrient level. Full article

The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells. Full article

Investigating dietary polyphenolic compounds as antitumor agents are rising due to the growing evidence of the close association between immunity and cancer. Cancer cells elude immune surveillance for enhancing their progression and metastasis utilizing various mechanisms. These mechanisms include the upregulation of programmed death-ligand 1 (PD-L1) expression and Epithelial-to-Mesenchymal Transition (EMT) cell phenotype activation. In addition to its role in stimulating normal embryonic development, EMT has been identified as a critical driver in various aspects of cancer pathology, including carcinogenesis, metastasis, and drug resistance. Furthermore, EMT conversion to another phenotype, Mesenchymal-to-Epithelial Transition (MET), is crucial in developing cancer metastasis. A central mechanism in the upregulation of PD-L1 expression in various cancer types is EMT signaling activation. In breast cancer (BC) cells, the upregulated level of PD-L1 has become a critical target in cancer therapy. Various signal transduction pathways are involved in EMT-mediated PD-L1 checkpoint overexpression. Three main groups are considered potential targets in EMT development; the effectors (E-cadherin and Vimentin), the regulators (Zeb, Twist, and Snail), and the inducers that include members of the transforming growth factor-beta (TGF-β). Meanwhile, the correlation between consuming flavonoid-rich food and the lower risk of cancers has been demonstrated. In BC, polyphenols were found to downregulate PD-L1 expression. This review highlights the effects of polyphenols on the EMT process by inhibiting mesenchymal proteins and upregulating the epithelial phenotype. This multifunctional mechanism could hold promises in the prevention and treating breast cancer. Full article

Time-restricted feeding (TRF) is becoming a popular way of eating in physically active populations, despite a lack of research on metabolic and performance outcomes as they relate to the timing of food consumption in relation to the time of exercise. The purpose of this study was to determine if the timing of feeding/fasting after exercise training differently affects muscle metabolic flexibility and response to an acute bout of exercise. Male C57BL/6 mice were randomized to one of three groups for 8 weeks. The control had ad libitum access to food before and after exercise training. TRF-immediate had immediate access to food for 6 h following exercise training and the TRF-delayed group had access to food 5-h post exercise for 6 h. The timing of fasting did not impact performance in a run to fatigue despite TRF groups having lower hindlimb muscle mass. TRF-delayed had lower levels of muscle HSL mRNA expression and lower levels of PGC-1α expression but displayed no changes in electron transport chain enzymes. These results suggest that in young populations consuming a healthy diet and exercising, the timing of fasting may not substantially impact metabolic flexibility and running performance. Full article

The gut microbiota is often mentioned as a “forgotten organ” or “metabolic organ”, given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a “good” microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut–lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases. Full article

We determined how vitamin D receptor (VDR) is linked to disease outcome in estrogen receptor-positive (ER+) breast cancer patients treated with tamoxifen (TAM). Breast cancer patients (n = 581) in four different datasets were divided into those expressing higher (above median) and lower levels of VDR in pretreatment ER+ tumors. Across all datasets, TAM-treated patients with higher pretreatment tumor VDR expression exhibited significantly longer recurrence-free survival. Ingenuity pathway analysis identified autophagy and unfolded protein response (UPR) as top differentially expressed pathways between high and low VDR-expressing ER+ cancers. Activation of VDR with vitamin D (VitD), either calcitriol or its synthetic analog EB1089, sensitized MCF-7-derived, antiestrogen-resistant LCC9 human breast cancer cells to TAM, and attenuated increased UPR and pro-survival autophagy. Silencing of VDR blocked these effects through the IRE1α-JNK pathway. Further, silencing of VDR impaired sensitivity to TAM in antiestrogen-responsive LCC1 cells, and prevented the effects of calcitriol and EB1089 on UPR and autophagy. In a preclinical mouse model, dietary VitD supplementation induced VDR activation and reduced carcinogen-induced ER+ mammary tumor incidence. In addition, IRE1α-JNK signaling was downregulated and survival autophagy was inhibited in mammary tumors of VitD-supplemented mice. Thus, activation of VDR is predictive of reduced risk of breast cancer recurrence in ER+ patients, possibly by inhibiting antiestrogen-promoted pro-survival autophagy. Full article

Insufficient blood levels of the neurohormone vitamin D are associated with increased risk of COVID-19 severity and mortality. Despite the global rollout of vaccinations and promising preliminary results, the focus remains on additional preventive measures to manage COVID-19. Results conflict on vitamin D’s plausible role in preventing and treating COVID-19. We examined the relation between vitamin D status and COVID-19 severity and mortality among the multiethnic population of the United Arab Emirates. Our observational study used data for 522 participants who tested positive for SARS-CoV-2 at one of the main hospitals in Abu Dhabi and Dubai. Only 464 of those patients were included for data analysis. Demographic and clinical data were retrospectively analyzed. Serum samples immediately drawn at the first hospital visit were used to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations through automated electrochemiluminescence. Levels < 12 ng/mL were significantly associated with higher risk of severe COVID-19 infection and of death. Age was the only other independent risk factor, whereas comorbidities and smoking did not contribute to the outcomes upon adjustment. Sex of patients was not an important predictor for severity or death. Our study is the first conducted in the UAE to measure 25(OH)D levels in SARS-CoV-2-positive patients and confirm the association of levels < 12 ng/mL with COVID-19 severity and mortality. Full article

As the most likely primary caregivers, mothers are an integral part of children’s social influence and are therefore greatly involved in shaping their children’s behaviors. The objectives were to determine the prospective associations between maternal and child diet quality and sedentary behaviors. This study, within the framework of a community-based intervention study, included 1130 children aged 8–10 years and their mothers. The study was carried out during two academic years (2012/2014) with a mean follow-up of 15 months. Exposure and outcome variables were measured at baseline and follow-up, respectively. Diet quality was assessed by the KIDMED questionnaire and the short Diet Quality Screener, respectively. Sedentary behaviors were determined by standardized questions of sedentary behaviors. Maternal consumption of fruits, vegetables, fish, legumes, pasta/rice, dairy products, nuts and baked goods were positively associated (p < 0.05) with the corresponding child behavior. Multiple linear regression models adjusted for sex, age, maternal education and intervention group revealed significant cross-sectional (p < 0.005) and prospective (p < 0.01) associations between maternal and child overall diet quality and sedentary behaviors. Maternal diet quality and sedentary behaviors were predictive for these lifestyle behaviors in children. Full article

In this study, a school nutrition program (SNP) that incorporates nutrition education and a healthy school canteen environment was developed to improve nutrition knowledge among intervention respondents and provide a healthier environment for them to practice healthy eating. In the current study, we evaluated the impacts of the SNP on eating behaviors, physical activity, body mass index-for-age (BAZ), and cognitive performance at pre-intervention, post-intervention, and 3-month follow-up points between intervention and comparison groups. This intervention study involved 523 primary school children (7–11 years old) from six selected schools in Batu Pahat District, Malaysia. Each respondent completed anthropometric and cognitive performance assessments and a set of standardized questionnaire at pre-intervention, post-intervention, and 3-month follow-up points. Multiple linear mixed model analysis was performed to determine the impacts of that SNP after being adjusted for covariates. After the program, the intervention group increased their frequency of breakfast, lunch, and dinner consumption and morning tea snacking and showed more frequent physical activity and better cognitive performance as compared to the comparison group overtime (p < 0.05). At 3-month follow-up, the intervention group showed lower BAZ scores than their comparison counterparts (p < 0.05). The SNP showed positive effects on eating behaviors, physical activity, BAZ, and cognitive performance in school children. Hence, the SNP is highly recommended for all primary school children. Full article

Ageing is associated with a reduction in muscle mass and strength, termed sarcopenia. Dietary protein is important for the maintenance of muscle mass through the promotion of muscle protein synthesis. However, protein is also reported to be a highly satiating nutrient. This raises concerns that protein intake for musculoskeletal health reasons in older adults may exacerbate age-related decreased appetite and may result in reduced energy and nutrient intake. This study aimed to investigate the effect of short-term protein supplementation and its timing (morning vs. evening), on energy and nutrient intake and appetite measures in middle-older age adults. Twenty-four 50–75 year olds were recruited to a randomised cross-over trial. In phase 1 (pre-supplementation) participants completed a food diary and reported hunger and appetite on three alternate days. During the second and third phases, participants consumed a 20 g whey protein gel (78 mL/368 kJ), for four days, either in the morning (after breakfast) or the evening (before bed), whilst completing the same assessments as phase 1. No differences in dietary intakes of energy, macronutrients and micronutrients were recorded when comparing the pre-supplementation phase to the protein supplementation phases, irrespective of timing (excluding the contribution of the protein supplement itself). Similarly, no differences were observed in self-reported feelings of hunger and appetite. In conclusion, a 20 g/day whey protein supplement given outside of meal-times did not alter habitual dietary intakes, hunger or appetite in this middle-older age adult population in the short-term. This approach may be a useful strategy to increasing habitual protein intake in the middle-older age population. Full article

Infants affected by Heiner syndrome (HS) display chronic upper or lower respiratory tract infections, including otitis media or pneumonia. Clinically, gastrointestinal signs and symptoms, anemia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. The pathogenetic mechanism underlying HS remains unexplained, but the formation of immune complexes and the cell-mediated reaction have been proposed. Patients usually outgrow this hypersensitivity within a few years. The aim of this review is to provide an updated overview on the current evidence on HS in children, with a critical approach on the still undefined points of this interesting disease. Finally, we propose the first structured diagnostic approach for HS. Full article