Nutrients, Volume 14, Issue 3 (February-1 2022) – 324 articles

Lipoteichoic acid (LTA) from Gram-positive bacteria exerts different immune effects depending on the bacterial source from which it is isolated. Lacticaseibacillus rhamnosus GG LTA (LGG-LTA) oral administration reduces UVB-induced immunosuppression and skin tumor development in mice. In the present work, we evaluate the immunomodulatory effect exerted by LGG-LTA in dendritic cells (DC) and T cells, both in vitro and in the gut-associated lymphoid tissue (GALT). During cell culture, LTA-stimulated BMDC increased CD86 and MHC-II expression and secreted low levels of pro and anti-inflammatory cytokines. Moreover, LTA-treated BMDC increased T cell priming capacity, promoting the secretion of IL-17A. On the other hand, in orally LTA-treated mice, a decrease in mature DC (lamina propria and Peyer’s patches) was observed. Concomitantly, an increase in IL-12p35 and IFN-γ transcription was presented (lamina propria and Peyer’s Patches). Finally, an increase in the number of CD103+ DC was observed in Peyer’s patches. Together, our data demonstrate that LGG-LTA activates DC and T cells. Moreover, we show that a Th1-biased immune response is triggered in vivo after oral LTA administration. These effects justify the oral LTA activity previously observed. Full article

Gut microbiota and biological rhythms are emerging as key factors in the modulation of several physiological and metabolic processes. However, little is known about their interaction and how this may affect host physiology and metabolism. Several studies have shown oscillations of gut microbiota that follows a circadian rhythmicity, but, in contrast, variations due to seasonal rhythms have not been sufficiently investigated yet. Thus, the goal of this study was to investigate the impact of different photoperiods, which mimic seasonal changes, on fecal microbiota composition and how this interaction affects diet-induced obesity development. To this aim, Fisher 344 male rats were housed under three photoperiods (L6, L12 and L18) and fed with standard chow diet or cafeteria diet (CAF) for 9 weeks. The 16S ribosomal sequencing of collected fecal samples was performed. The photoperiod exposure significantly altered the fecal microbiota composition under L18, especially in CAF-fed rats. Moreover, these alterations were associated with changes in body weight gain and different fat parameters. These findings suggest a clear impact of seasonal rhythms on gut microbiota, which ultimately translates into different susceptibilities to diet-induced obesity development. This is the first time to our knowledge that the photoperiod impact on gut microbiota composition has been described in an obesity context although further studies are needed in order to elucidate the mechanisms involved. Full article

The composition of the gut microbiota and their metabolites are associated with cardiometabolic health and disease risk. Intake of dietary fibers, including resistant starch (RS), has been shown to favorably affect the health of the gut microbiome. The aim of this research was to measure changes in the gut microbiota and fecal short-chain fatty acids as part of a randomized, crossover supplemental feeding study. Fifty participants (68% female, aged 40 ± 13 years, BMI 24.5 ± 3.6 kg/m²) completed this study. Potato dishes (POT) contained more RS than refined grain dishes (REF) (POT: 1.31% wet basis (95% CI: 0.94, 1.71); REF: 0.73% wet basis (95% CI: 0.34, 1.14); p = 0.03). Overall, potato dish consumption decreased alpha diversity, but beta diversity was not impacted. Potato dish consumption was found to increase the abundance of Hungatella xylanolytica, as well as that of the butyrate producing Roseburia faecis, though fecal butyrate levels were unchanged. Intake of one potato-based side dish per day resulted in modest changes in gut microbiota composition and diversity, compared to isocaloric intake of refined grains in healthy adults. Studies examining foods naturally higher in RS are needed to understand microbiota changes in response to dietary intake of RS and associated health effects. Full article

Choline requirements are high in the rapidly growing fetus and preterm infant, mainly serving phosphatidylcholine (PC) synthesis for parenchymal growth and one-carbon metabolism via betaine. However, choline metabolism in critical organs during rapid growth is poorly understood. Therefore, we investigated the kinetics of D9-choline and its metabolites in the liver, plasma, brain and lung in 14 d old rats. Animals were intraperitoneally injected with 50 mg/kg D9-choline chloride and sacrificed after 1.5 h, 6 h and 24 h. Liver, plasma, lungs, cerebrum and cerebellum were analyzed for D9-choline metabolites, using tandem mass spectrometry. In target organs, D9-PC and D9-betaine comprised 15.1 ± 1.3% and 9.9 ± 1.2% of applied D9-choline at 1.5 h. D9-PC peaked at 1.5 h in all organs, and decreased from 1.5–6 h in the liver and lung, but not in the brain. Whereas D9-labeled PC precursors were virtually absent beyond 6 h, D9-PC increased in the brain and lung from 6 h to 24 h (9- and 2.5-fold, respectively) at the expense of the liver, suggesting PC uptake from the liver via plasma rather than local synthesis. Kinetics of D9-PC sub-groups suggested preferential hepatic secretion of linoleoyl-PC and acyl remodeling in target organs. D9-betaine showed rapid turnover and served low-level endogenous (D3-)choline synthesis. In conclusion, in neonatal rats, exogenous choline is rapidly metabolized to PC by all organs. The liver supplies the brain and lung directly with PC, followed by organotypic acyl remodeling. A major fraction of choline is converted to betaine, feeding the one-carbon pool and this must be taken into account when calculating choline requirements. Full article

Changes in consumption of sugar sweetened beverage (SSBs) have been associated with increased body mass index (BMI), but little work has evaluated the effect on waist circumference (WC) and body fat percentage during adolescence, a period characterized by rapid growth and change in dietary behaviors. We examined the relationship of changes in SSB intake and changes in adiposity over two years in 464 Mexican adolescents. Food frequency questionnaires were used to sum intake of regular soda, coffee with sugar, tea with sugar, sweetened water with fruit, chocolate milk, corn atole, and a sweetened probiotic milk beverage. Linear regression models were used to estimate the associations of changes in SSBs with changes in BMI, body fat percentage, and WC, adjusting for sex, socioeconomic status, screen time, physical activity, age, and change in age. Adolescents who increased their daily SSB intake by >2 serving had a −2.72% higher body fat percentage (95% CI: 0.61, 4.82); a 1–2 serving increase was associated with a 2.49 cm increase (95% CI: 0.21, 4.76) in WC compared with those with no change in intake. Within an adolescent sample, changes in SSB intake were related to concomitant changes in body fat percentage and WC, but not BMI. Full article

S-adenosylhomocysteine (SAH) is a risk factor of cardiovascular diseases and atherosclerosis. However, the causal association between SAH and atherosclerosis is still uncertain. In the present study, heterozygous SAH hydrolase (SAHH^+/−) knockout mice were bred with apolipoprotein E-deficient mice to produce ApoE^−/−/SAHH^+/− mice. At 8 weeks of age, these mice were fed on AIN-93G diets added with or without betaine (4 g betaine/100 g diet) for 8 weeks. Compared with ApoE^−/−/SAHH^WT mice, SAHH deficiency caused an accumulation of plasma SAH concentration and a decrease in S-adenosylmethionine (SAM)/SAH ratio as well as plasma homocysteine levels. Betaine supplementation lowered SAH levels and increased SAM/SAH ratio and homocysteine levels in ApoE^−/−/SAHH^+/− mice. Furthermore, SAHH deficiency promoted the development of atherosclerosis, which was reduced by betaine supplementation. The atheroprotective effects of betaine on SAHH-deficiency-promoted atherosclerosis were associated with inhibition of NFκB inflammation signaling pathway and inhibition of proliferation and migration of smooth muscle cells. In conclusion, our results suggest that betaine supplementation lowered plasma SAH levels and protected against SAHH-deficiency-promoted atherosclerosis through repressing inflammation and proliferation and migration of smooth muscle cells. Full article

Identifying and quantifying the beneficial molecules contained in nutraceuticals is essential to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol^®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lycopene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/β-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lycopene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol^® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol^® lycopene extract increased ALP and β-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p < 0.05 respectively). In conclusion, despite both techniques showing similar final results, UV/VIS spectrophotometer is preferable to HPLC due to its cheap, rapid, and accurate results, as well as for the opportunity to analyze lycopene-loaded micelles. The extraction and release of lycopene to bone cells positively influences the differentiation of osteoblasts and increases the expression of the ALP and β-catenin proteins. As a consequence, as a lycopene-rich sauce, Osteocol^® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors. Full article

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters. Full article

Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer. The pancreas uptakes molecular iodine (I₂), which has anti-inflammatory and antioxidant effects. The present work analyzes whether oral I₂ supplementation prevents the pancreatic alterations promoted by low doses of streptozotocin (STZ). CD1 mice (12 weeks old) were divided into the following groups: control; STZ (20 mg/kg/day, i.p. for five days); I₂ (0.2 mg/Kg/day in drinking water for 15 days); and combined (STZ + I₂). Inflammation (Masson’s trichrome and periodic acid–Schiff stain), hyperglycemia, decreased β-cells and increased α-cells in pancreas were observed in male and female animals with STZ. These animals also showed pancreatic increases in immune cells and inflammation markers as tumor necrosis factor-alpha, transforming growth factor-beta and inducible nitric oxide synthase with a higher amount of activated pancreatic stellate cells (PSCs). The I₂ supplement prevented the harmful effect of STZ, maintaining normal pancreatic morphometry and functions. The elevation of the nuclear factor erythroid-2 (Nrf2) and peroxisome proliferator-activated receptor type gamma (PPARγ) contents was associated with the preservation of normal glycemia and lipoperoxidation. In conclusion, a moderated supplement of I₂ prevents the deleterious effects of STZ in the pancreas, possibly through antioxidant and antifibrotic mechanisms including Nrf2 and PPARγ activation. Full article

Whole grains are a vital part of a healthy diet, yet there are insufficient data on the whole-grain content of commercial food products. The purpose of this research is to examine the long-term change in (1) measured whole grains in food products, (2) Whole Grain Stamp usage and (3) the prominence of whole-grain ingredients and product categories, across the United States and Latin America. These changes were quantified by analyzing the Oldways Whole Grains Council’s (WGC) Stamped Product Database from 2007 to 2020. Mean whole grains increased 36–76%, from 19 grams to 25.8 grams per serving in the U.S. and 18.1 grams to 31.9 grams per serving in Latin America. Whole Grain Stamp usage worldwide has increased from 250 products in 2005 to more than 13,000 products in 2020. These findings suggest that manufacturers are increasing the percentage of the grain that is whole in their products and developing more whole-grain products for consumers, thus providing an opportunity for consumers to meet national-level whole-grain recommendations. Full article

Ferrous sulphate (FS) is widely used as an iron supplement to treat iron deficiency (ID), but is known to induce inflammation causing gastric side-effects resulting in poor adherence to supplement regimens. Curcumin, a potent antioxidant, has been reported to suppress inflammation via down regulation of NF-κB. The aim of the present double blind, placebo-controlled randomised trial was to assess whether co-administration of FS with a formulated, bioavailable form of curcumin (HydroCurc™) could reduce systemic inflammation and/or gastrointestinal side-effects. This study recruited 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54), randomly allocated to one of five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Completed questionnaires and blood samples were collected from all participants at baseline (day 1), mid-point (day 21), and at end-point (day 42). Results showed a significant reduction in IL-6 in the FS65_Curc group (0.06 pg/mL ± 0.02, p = 0.0073) between the mid-point and end-point. There was also a significant reduction in mean plasma TNF levels in the FS65_Curc (0.65 pg/mL ± 0.17, p = 0.0018), FS65_Plac (0.39 pg/mL ± 0.15, p = 0.0363), and FS18_Curc (0.35 pg/mL ± 0.13, p = 0.0288) groups from mid-point to end-point. A significant increase was observed in mean plasma TBARS levels (0.10 µM ± 0.04, p = 0.0283) in the F18_Plac group from baseline to end-point. There was a significant association with darker stools between FS0_Plac vs. FS65_Plac (p = 0.002, Fisher’s exact test) suggesting that high iron dose in the absence of curcumin leads to darker stools. A reduction in inflammation-related markers in response to co-administering supplemental iron alongside formulated curcumin suggests a reduction in systemic inflammation. This supplementation approach may therefore be a more cost effective and convenient alternative to current oral iron-related treatments, with further research to be conducted. Full article

This study aimed to describe the intake and food sources of macronutrients in vegetarian and non-vegetarian adolescent females. Cross-sectional data was collected between February and September 2019. Adolescent females, aged 15 to 18 years old, were recruited throughout New Zealand. Intakes were assessed via two 24-h diet recalls, adjusted to represent usual intake using the multiple source method. Of the 254 participants, 38 self-identified as vegetarian. Vegetarians had similar carbohydrate and fat intakes compared to non-vegetarians; however, their protein intakes were 2.1% kJ lower (95% confidence interval (CI) −3.0 to −1.1%). Vegetarians also consumed 1.1% kJ less saturated fat (95% CI –2.1 to −0.1%), 1.3% kJ (95% CI 0.7 to 1.9) more polyunsaturated fat, and 5 g/day (95% CI 1.8 to 8.0) more fiber than non-vegetarians. When consumed, bread-based dishes and discretionary foods were the highest sources of energy, fat, and carbohydrate in both vegetarians and non-vegetarians. This suggests that some adolescents, including vegetarians, were obtaining high amounts of fat and carbohydrate from food groups associated with poorer dietary quality. We recommend further research to assess how the changing food environment is influencing vegetarian eating patterns and their associations with health outcomes in the wider population. Full article

This study aimed to investigate the direct influence of a decrease in the cellular thiamin level, before the onset of anorexia (one of the symptoms of thiamin deficiency) on glycogen metabolism and the AMP-activated protein kinase (AMPK) activation levels in skeletal muscle at rest and in response to exercise. Male Wistar rats were classified as the control diet (CON) group or the thiamin-deficient diet (TD) group and consumed the assigned diets for 1 week. Skeletal muscles were taken from the rats at rest, those that underwent low-intensity swimming (LIS), or high-intensity intermittent swimming (HIS) conducted immediately before dissection. There were no significant differences in food intake, locomotive activity, or body weight between groups, but thiamin pyrophosphate in the skeletal muscles of the TD group was significantly lower than that of the CON group. Muscle glycogen and lactate levels in the blood and muscle were equivalent between groups at rest and in response to exercise. The mitochondrial content was equal between groups, and AMPK in the skeletal muscles of TD rats was normally activated by LIS and HIS. In conclusion, with a lowered cellular thiamin level, the exercise-associated glycogen metabolism and AMPK activation level in skeletal muscle were normally regulated. Full article

It is unclear how vegetarian dietary patterns influence plasma metabolites involved in biological processes regulating chronic diseases. We sought to identify plasma metabolic profiles distinguishing vegans (avoiding meat, eggs, dairy) from non-vegetarians (consuming ≥28 g/day red meat) of the Adventist Health Study-2 cohort using global metabolomics profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS). Differences in abundance of metabolites or biochemical subclasses were analyzed using linear regression models, adjusting for surrogate and confounding variables, with cross-validation to simulate results from an independent sample. Random forest was used as a learning tool for classification, and principal component analysis was used to identify clusters of related metabolites. Differences in covariate-adjusted metabolite abundance were identified in over 60% of metabolites (586/930), after adjustment for false discovery. The vast majority of differentially abundant metabolites or metabolite subclasses showed lower abundance in vegans, including xanthine, histidine, branched fatty acids, acetylated peptides, ceramides, and long-chain acylcarnitines, among others. Many of these metabolite subclasses have roles in insulin dysregulation, cardiometabolic phenotypes, and inflammation. Analysis of metabolic profiles in vegans and non-vegetarians revealed vast differences in these two dietary groups, reflecting differences in consumption of animal and plant products. These metabolites serve as biomarkers of food intake, many with potential pathophysiological consequences for cardiometabolic diseases. Full article

Excess sugar consumption can lead to noncommunicable diseases (NCDs) such as type 2 diabetes. Increasingly, ultra-processed foods (UPF) are suspected to be great contributors to free sugars intake in the population’s diet. Thus, the aim of this study was to investigate the association between UPF consumption and free sugars intake in the Canadian population. We used data from one 24 h-recall of the nationally representative 2015 Canadian Community Health Survey–Nutrition (CCHS). Food items were classified according to the NOVA system, and to estimate free sugars intake, we used the University of Toronto’s Food Label Information Program (FLIP) 2017 database. Results: Almost half of the population’s energy intake (45.7%) came from UPF. On average, 221.5 kcal/day came from free sugars, and most of these calories (71.5%) came from UPF. Public health policies aiming to decrease consumption of UPF should be a priority considering their important contribution to sugar intake in the population. Full article

A Mediterranean-style healthy eating pattern (MED-HEP) supports metabolic health, but the utility of including low-glycemic index (GI) foods to minimize postprandial glucose excursions remain unclear. Therefore, we investigated the relative contribution of GI towards improvements in postprandial glycemia and glycemic variability after adopting a MED-HEP. We conducted a randomized, controlled dietary intervention, comparing high- versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of adults at risk for type 2 diabetes. For 12 weeks, participants consumed either a low-GI or high-GI MED-HEP. We assessed postprandial plasma glucose and insulin responses to high- or low-GI meals, and daily glycemic variability via continuous glucose monitoring at baseline and post-intervention. One hundred sixty adults (86 females, 74 males; aged 55 ± 11 y, BMI 31 ± 3 kg/m², mean ± SD) with ≥two metabolic syndrome traits completed the intervention. Postprandial insulin concentrations were greater after the high-GI versus the low-GI test meals at baseline (p = 0.004), but not post-intervention (p = 0.17). Postprandial glucose after the high-GI test meal increased post-intervention, being significantly higher than that after the low-GI test meal (35%, p < 0.001). Average daily glucose concentrations decreased in both groups post-intervention. Indices of 24-h glycemic variability were reduced in the low-GI group as compared to baseline and the high-GI intervention group. These findings suggest that low-GI foods may be an important feature within a MED-HEP. Full article

Most studies disregard long-term dairy consumption behaviour and how it relates to mortality. We examined four different types of long-term milk consumption, namely whole milk, reduced fat milk, skim milk and soy milk, in relation to mortality among adults diagnosed with cardiovascular disease (CVD). A retrospective population-based study was conducted in Australia (the 45 and Up Study) linking baseline (2006–2009) and follow-up data (2012–2015) to hospitalisation and mortality data up to 30 September 2018. A total of 1,101 deaths occurred among 7236 participants with CVD over a mean follow-up of 8.4 years. Males (Hazard Ratio, HR = 0.69, 95% CI (0.54; 0.89)) and females (HR = 0.59 (0.38; 0.91)) with long-term reduced fat milk consumption had the lowest risk of mortality compared to counterparts with long-term whole milk consumption. Among participants with ischemic heart disease, males with a long-term reduced fat milk consumption had the lowest risk of mortality (HR = 0.63, 95% CI: 0.43; 0.92). We conclude that among males and females with CVD, those who often consume reduced fat milk over the long-term present with a 31–41% lower risk of mortality than those who often consume whole milk, supporting dairy advice from the Heart Foundation of replacing whole milk with reduced fat milk to achieve better health. Full article

This study evaluated the changes in bone mineral density (BMD) and serum lipids across the first postpartum year in lactating women compared to never-pregnant controls, and the influence of physical activity (PA). The study also explored whether N-telopeptides, pyridinoline, and deoxypyridinoline in urine serve as biomarkers of bone resorption. A cohort of 18 initially lactating postpartum women and 16 never pregnant controls were studied. BMD (dual energy X-ray absorptiometry), serum lipid profiles, and PA (Baecke PA Questionnaire) were assessed at baseline (4–6 weeks postpartum), 6 months, and 12 months. Postpartum women lost 5.2 ± 1.4 kg body weight and BMD decreased by 1.4% and 3.1% in the total body and dual-femur, respectively. Furthermore, BMDdid not show signs of rebound. Lipid profiles improved, with increases in high-density lipoprotein-cholesterol (HDL-C) and decreases in low-density lipoprotein cholesterol (LDL-C) and the cholesterol/HDL-C ratio at 12 months (vs. baseline). These changes were not influenced by lactation, but the fall the Cholesterol/HDL-C ratio was influenced by leisure-time (p = 0.051, time X group) and sport (p = 0.028, time effect) PA. The decrease in BMD from baseline to 12 months in total body and dual femur, however, was greater in those who continued to breastfeed for a full year compared to those who stopped at close to 6 months. Urinary markers of bone resorption, measured in a subset of participants, reflect BMD loss, particularly in the dual-femur, and may reflect changes bone resorption before observed changes in BMD. Results provide support that habitual postpartum PA may favorably influence changes in serum lipids but not necessarily BMD. The benefit of exercise and use of urinary biomarkers of bone deserves further exploration. Full article

No consensus currently exists on the appropriate age for the introduction of complementary feeding (CF). In this paper, a systematic review is conducted that investigates the effects of starting CF in breastfed and formula-fed infants at 4, 4–6, or 6 months of age (i) on growth at 12 months of age, (ii) on the development of overweight/obesity at 3–6 years of age, (iii) on iron status, and (iv) on the risk of developing (later in life) type 2 diabetes mellitus (DM2) and hypertension. An extensive literature search identified seven studies that evaluated the effects of the introduction of CF at the ages in question. No statistically significant differences related to the age at which CF is started were observed in breastfed or formula-fed infants in terms of the following: iron status, weight, length, and body mass index Z-scores (zBMI) at 12 months, and development of overweight/obesity at 3 years. No studies were found specifically focused on the age range for CF introduction and risk of DM2 and hypertension. Introducing CF before 6 months in healthy term-born infants living in developed countries is essentially useless, as human milk (HM) and formulas are nutritionally adequate up to 6 months of age. Full article

Creatine is an important energy metabolite that is concentrated in tissues such as the muscles and brain. Creatine is reversibly converted to creatine phosphate through a reaction with ATP or ADP, which is catalyzed by the enzyme creatine kinase. Dietary supplementation with relatively large amounts of creatine monohydrate has been proven as an effective sports supplement that can enhances athletic performance during acute high-energy demand physical activity. Some side effects have been reported with creatine monohydrate supplementation, which have stimulated research into new potential molecules that could be used as supplements to potentially provide bioavailable creatine. Recently, a popular supplement, creatyl-l-leucine, has been proposed as a potential dietary ingredient that may potentially provide bioavailable creatine. This study tests whether creatyl-l-leucine is a bioavailable compound and determines whether it can furnish creatine as a dietary supplement. Rats were deprived of dietary creatine for a period of two weeks and then given one of three treatments: a control AIN-93G creatine-free diet, AIN-93G supplemented with creatine monohydrate or AIN-93G with an equimolar amount of creatyl-l-leucine supplement in the diet for one week. When compared to the control and the creatine monohydrate-supplemented diet, creatyl-l-leucine supplementation resulted in no bioaccumulation of either creatyl-l-leucine or creatine in tissue. Full article

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, iron mobilization, connective tissue crosslinking, antioxidant defense, melanin synthesis, blood clotting, and neuron peptide maturation. Increasing lines of evidence obtained from studies of cell culture, animals, and human genetics have demonstrated that dysregulation of copper metabolism causes heart disease, which is the leading cause of mortality in the US. Defects of copper homeostasis caused by perturbed regulation of copper chaperones or copper transporters or by copper deficiency resulted in various types of heart disease, including cardiac hypertrophy, heart failure, ischemic heart disease, and diabetes mellitus cardiomyopathy. This review aims to provide a timely summary of the effects of defective copper homeostasis on heart disease and discuss potential underlying molecular mechanisms. Full article

Multidrug resistance (MDR) to anticancer drugs remains a serious obstacle to the success of cancer chemotherapy. Resveratrol, a polyphenol, present in natural products exerts anticancer activity and acts as a potential MDR inhibitor in various drug-resistant cancer cells. In the process of resensitization of drug-resistant cancer cells, resveratrol has been shown to interfere with ABC transporters and drug-metabolizing enzymes, increase DNA damage, inhibit cell cycle progression, and induce apoptosis and autophagy, as well as prevent the induction of epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). This review summarizes the mechanisms by which resveratrol counteracts MDR in acquired drug-resistant cancer cell lines and provides a critical basis for understanding the regulation of MDR as well as the development of MDR-inhibiting drugs. Full article

In term infants it is recommended to introduce solids between the 17th and 26th week of life, whereas data for preterm infants are missing. In a prospective, two-arm interventional study we investigated longitudinal growth of VLBW infants after early (10–12th) or late (16–18th) week of life, corrected for term, introduction of standardized complementary food. Primary endpoint was height at one year of age, corrected for term, and secondary endpoints were other anthropometric parameters such as weight, head circumference, BMI, and z-scores. Among 177 infants who underwent randomization, the primary outcome could be assessed in 83 (93%) assigned to the early and 83 (94%) to the late group. Mean birthweight was 941 (SD ± 253) g in the early and 932 (SD ± 256) g in the late group, mean gestational age at birth was 27 + 1/7 weeks in both groups. Height was 74.7 (mean; SD ± 2.7) cm in the early and 74.4 cm (mean; SD ± 2.8; n.s.) cm in the late group at one year of age, corrected for term. There were no differences in anthropometric parameters between the study groups except for a transient effect on weight z-score at 6 months. In preterm infants, starting solids should rather be related to neurological ability than to considerations of nutritional intake and growth. Full article

This study aimed to investigate the relationship between meal frequency and obesity in Chinese adults aged 18 to 59 years. The data came from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance (CACDNS 2015) and provincial dietary environment data from the 2015 National Statistical Yearbook. A total of 34,206 adults aged 18 to 59 who took part in the diet survey were selected as the study participants. A two-level multivariate logistic regression model was used to adjust for the socioeconomic and nutritional status of individuals. For parameter estimation, a numerical integral approach was used to analyze the relationship between meal frequency (including meals at home, the workplace or school dining halls, and eating away from home) and obesity. A two-level “provincial–individual” logistic multivariate regression analysis was performed with obesity as the dependent variable. The two-level multivariate analysis of variance model fitting results showed that after adjusting for the effects of gender, age, occupation, education, marital status, family per capita annual income, provincial gross domestic product (GDP), restaurant industry turnover, consumer price index of EAFH food, and energy intake, the frequency of eating at home was not associated with obesity (all p > 0.05); the frequency of eating at dining halls ≥1 to <2 times per day (OR = 0.784, p = 0.0122) showed a negative association with obesity; the frequency of eating away from home < 1 times per day and ≥1 to <2 times per day were positively correlated with obesity (<1 time per day: OR = 1.123, p = 0.0419; ≥1 to <2 times per day: OR = 1.249, p = 0.0022). The results of the two-level random-intercept logistic multivariate mixed-effects prediction model for obesity in adults aged 18 to 59 years showed that no statistical association was noticed between the frequency of eating at home and obesity in adults aged 18 to 59 years. However, adults who ate out < 1 time and ≥1 to <2 times a day showed higher risks of obesity than those who did not eat out, with OR = 1.131 (95% CI 1.012–1.264) and OR = 1.258 (95% CI 1.099–1.440), while adults who ate at school and workplace dining halls ≥1 to <2 times a day may have a reduced risk of obesity, with OR = 0.790 (95% CI 0.656–0.951). This result could not be found based on the definition of eating out in previous studies. Therefore, it is recommended to exclude nonprofit collective canteens such as school and workplace dining halls from the definition of eating away from home, and to redefine eating out in terms of health effects. At the same time, it is also recommended to strengthen collective nutritional interventions around canteens, improve the nutritious meal system in school and workplace canteens, and create healthy canteens. Full article

The hepatic adiponectin and farnesoid X receptor (FXR) signaling pathways play multiple roles in modulating lipid and glucose metabolism, reducing hepatic inflammation and fibrosis, and altering various metabolic targets for the management of non-alcoholic fatty liver disease (NAFLD). Alisma orientale (AO, Ze xie in Chinese and Taeksa in Korean) is an herbal plant whose tubers are enriched with triterpenoids, which have been reported to exhibit various bioactive properties associated with NAFLD. Here, the present study provides a preclinical evaluation of the biological functions and related signaling pathways of AO extract for the treatment of NAFLD in a Western diet (WD)-induced mouse model. The findings showed that AO extract significantly reversed serum markers (liver function, lipid profile, and glucose) and improved histological features in the liver sections of mice fed WD for 52 weeks. In addition, it also reduced hepatic expression of fibrogenic markers in liver tissue and decreased the extent of collagen-positive areas, as well as inhibited F4/80 macrophage aggregation and inflammatory cytokine secretion. The activation of adiponectin and FXR expression in hepatic tissue may be a major mechanistic signaling cascade supporting the promising role of AO in NAFLD pharmacotherapy. Collectively, our results demonstrated that AO extract improves non-alcoholic steatohepatitis (NASH) resolution, particularly with respect to NASH-related fibrosis, along with the regulation of liver enzymes, postprandial hyperglycemia, hyperlipidemia, and weight loss, probably through the modulation of the hepatic adiponectin and FXR pathways. Full article

Background: Little is known about the effects of dietary quality on the risk of ischemic stroke among Southwest Chinese, and evidence from prospective studies is needed. We aimed to evaluate the associations of ischemic stroke with dietary quality assessed by the Chinese Diet Balance Index 2016 (DBI-2016). Methods: The Guizhou Population Health Cohort Study (GPHCS) recruited 9280 residents aged 18 to 95 years from 12 areas in Guizhou Province, Southwest China. Baseline investigations, including information collections of diet and demographic characteristics, and anthropometric measurements were performed from 2010 to 2012. Dietary quality was assessed by using DBI-2016. The primary outcome was incident ischemic stroke diagnosed according to the International Classification of Diseases 10th revision (ICD-10) until December 2020. Data analyzed in the current study was from 7841 participants with complete information of diet assessments and ischemic stroke certification. Cox proportional hazards models were used to estimate the risk of ischemic stroke associated with dietary quality. Results: During a median follow-up of 6.63 years (range 1.11 to 9.53 years), 142 participants were diagnosed with ischemic stroke. Participants with ischemic stroke had a more excessive intake of cooking oils, alcoholic beverages, and salt, and had more inadequacy in meats than those without ischemic stroke. (p < 0.05). Compared with participants in the lowest quartile (Q1), those in the highest quartile (Q4) of the higher bound score (HBS) and of the dietary quality distance (DQD) had an elevated risk for ischemic stroke, with the corresponding hazard ratios (HRs) of 3.31 (95%CI: 1.57–6.97) and 2.26 (95%CI: 1.28–4.00), respectively, after adjustment for age, ethnic group, education level, marriage status, smoking and waist circumference, and the medical history of diabetes and hypertension at baseline. In addition, excessive intake levels (score 1–6) of cooking oils, excessive intake levels (score 1–6) of salt, and inadequate intake levels (score −12 to −7) of dietary variety were positively associated with an increased risk for ischemic stroke, with the multiple HRs of 3.00 (95%CI: 1.77–5.07), 2.03 (95%CI: 1.33–3.10) and 5.40 (95%CI: 1.70–17.20), respectively. Conclusions: Our results suggest that unfavorable dietary quality, including overall excessive consumption, excessive intake of cooking oils and salt, or under adequate dietary diversity, may increase the risk for ischemic stroke. Full article