Phenylketonuria (PKU) is treated with dietary restrictions and sometimes tetrahydrobiopterin (BH4). PKU patients are at risk for developing micronutrient deficiencies, such as vitamin B12 and folic acid, likely due to their diet. Tyrosinemia type 1 (TT1) is similar to PKU in both pathogenesis and treatment. TT1 patients follow a similar diet, but nutritional deficiencies have not been investigated yet. In this retrospective study, biomarkers of micronutrients in TT1 and PKU patients were investigated and outcomes were correlated to dietary intake and anthropometric measurements from regular follow-up measurements from patients attending the outpatient clinic. Data was analyzed using Kruskal–Wallis, Fisher’s exact and Spearman correlation tests. Furthermore, descriptive data were used. Overall, similar results for TT1 and PKU patients (with and without BH4) were observed. In all groups high vitamin B12 concentrations were seen rather than B12 deficiencies. Furthermore, all groups showed biochemical evidence of vitamin D deficiency. This study shows that micronutrients in TT1 and PKU patients are similar and often within the normal ranges and that vitamin D concentrations could be optimized. Full article

Cirrhosis patients often have abnormal glucose metabolism. We investigated the effects of a late-evening snack (LES) with branched-chain amino acid-enriched nutrients (BCAA-EN) on glucose metabolism in cirrhosis patients. LES with BCAA-EN was administered for 1 week in 13 patients with cirrhosis and hypoalbuminemia. Blood glucose (BG) levels were measured every 15 min. The patients were divided into two groups based on BG levels: group 1 (G1, n = 11): nocturnal BG levels <200 mg/dL and group 2 (G2, n = 2): nocturnal BG levels ≥200 mg/dL. G1 had nocturnal BG levels <200 mg/dL, whereas G2 had nocturnal BG levels ≥200 mg/dL. The average BG levels did not significantly change after BCAA-EN administration in G1 (before 91.9 ± 29.0 mg/dL; after 89.0 ± 24.3 mg/dl). However, the average BG levels significantly increased after BCAA-EN administration in G2 (before 153.6 ± 43.3 mg/dL; after 200.9 ± 59.7 mg/dL) (p < 0.01). The glycated albumin level (16.6 ± 0.9% vs. 16.2 ± 2.1%), fasting immunoreactive insulin (F-IRI) level (53.9 ± 34.0 μU/mL vs. 16.5 ± 11.0 μU/mL), and homeostasis model assessment of insulin resistance (HOMA-IR) score (17.85 ± 10.58 vs. 4.02 ± 2.59) were significantly higher in G2 than in G1 (p < 0.05, p < 0.05, and p < 0.01, respectively). The quantitative insulin sensitivity check indices (0.32 ± 0.03 vs. 0.27 ± 0.02) were significantly higher in G1 than in G2 (p < 0.01). One patient in G2 was obese and had type 2 diabetes. The other patient was obese and had a high HOMA-IR score and F-IRI level. A LES with BCAA-EN does not inhibit overt diabetes in most cirrhosis patients. However, close attention should be paid to fluctuations in BG levels in cirrhosis patients who present with obesity and severe insulin resistance. Full article

Effects of meal frequency on blood glucose levels and glucose metabolism were evaluated over 3 days in adult males with normal glucose tolerance (NGT, n = 9) or impaired fasting glucose (IFG, n = 9) in a randomized, crossover comparison study. Subjects were provided with an isocaloric diet 3 times daily (3M) or 9 times daily (9M). Blood glucose was monitored on Day 3 using a continuous glucose monitoring system, and subjects underwent a 75-g oral glucose tolerance test (OGTT) on Day 4. Daytime maximum blood glucose, glucose range, duration of glucose ≥180 mg/dL, and nighttime maximum glucose were significantly lower in the NGT/9M condition than in the NGT/3M condition. Similar findings were observed in the IFG subjects, with a lower daytime and nighttime maximum glucose and glucose range, and a significantly higher daytime minimum glucose in the 9M condition than in the 3M condition. The OGTT results did not differ significantly between NGT/3M and NGT/9M conditions. In contrast, the incremental area under the curve tended to be lower and the maximum plasma glucose concentration was significantly lower in the IFG/9M condition than in the IFG/3M condition. In IFG subjects, the 9M condition significantly improved glucose metabolism compared with the 3M condition. Higher meal frequency may increase glucagon-like peptide 1 secretion and improve insulin secretion. Full article

There are limited studies examining water consumption among individuals in hot climates. We assessed the daily total water intake from plain water, other beverages, and food in a nationally representative sample of children and adolescents aged 6–18 years in the United Arab Emirates. Total water intake was compared against the recommendations of the Institute of Medicine and the European Food Safety Authority. Sociodemographic information, 24 h dietary recall, physical activity levels, and anthropometric data were collected from 527 participants. The mean ± SE of total water intake was 1778.4 ± 33.8 mL/day. Plain drinking water was the largest contributor to total water intake (51.6%), followed by food (27.3%). Sugar-sweetened beverages constituted 13.9% of water intake. The proportion of participants who met the Institute of Medicine recommendations ranged from 15% (males aged 14–18) to 25% (children aged 6–8). The proportion of participants who met the European Food Safety Authority recommendations ranged from 31% (females aged 14–18) to 36% (males aged 14–18). The water-to-energy ratio was 1.0–1.15 L/1000 kcal, meeting recommendations. The majority of participants failed to meet water intake recommendations, highlighting the need for targeted interventions to promote increased water consumption among children and adolescents. Full article

Helicobacter pylori infection is common in low-income countries. It has been associated with iron deficiency and reduced efficacy of iron supplementation. Whether H. pylori infection affects iron absorption from fortified and biofortified foods is unclear. Our objective was to assess whether asymptomatic H. pylori infection predicts dietary iron bioavailability in women and children, two main target groups of iron fortification programs. We did a pooled analysis of studies in women of reproductive age and preschool children that were conducted in Benin, Senegal and Haiti using stable iron isotope tracers to measure erythrocyte iron incorporation. We used mixed models to assess whether asymptomatic H. pylori infection predicted fractional iron absorption from ferrous sulfate, ferrous fumarate or NaFeEDTA, controlling for age, hemoglobin, iron status (serum ferritin), inflammation (C-reactive protein), and test meal. The analysis included 213 iron bioavailability measurements from 80 women and 235 measurements from 90 children; 51.3% of women and 54.4% of children were seropositive for H. pylori. In both women and children, hemoglobin (Hb), serum ferritin (SF), and C-reactive protein (CRP) did not differ between the seropositive and seronegative groups. Geometric mean (95% CI) fractional iron absorption (%), adjusted for SF, was 8.97% (7.64, 10.54) and 6.06% (4.80, 7.67) in H. pylori positive and negative women (p = 0.274), and 9.02% (7.68, 10.59) and 7.44% (6.01, 9.20) in H. pylori positive and negative children (p = 0.479). Our data suggest asymptomatic H. pylori infection does not predict fractional iron absorption from iron fortificants given to preschool children or young women in low-income settings. Full article

Patients with obesity and type 2 diabetes mellitus (T2DM) are regarded to have reduced serum magnesium (Mg) concentrations. We aimed to assess the changes in serum Mg concentrations at 12-month follow-up in patients, with and without T2DM, who underwent one anastomosis gastric bypass surgery. Overall, 50 patients (80% female, age 42.2 (12.5) years) with morbid obesity (mean baseline BMI 43.8 (4.3) kg/m²) were included in the analysis. Half of the included patients had T2DM diagnosed at baseline, and these patients showed lower serum Mg concentration (0.78 (0.07)) vs. 0.83 (0.05) mmol/L; p = 0.006), higher blood glucose levels (129.9 (41.3) vs. 87.6 (8.1) mg/dL; p < 0.001) as well as HbA1c concentrations (6.7 (1.4) vs. 5.3 (0.5)%; p < 0.001). During follow-up, BMI and glucose levels showed a decrease; however, serum Mg levels remained stable. At baseline 42% of patients were found to be Mg deficient, which was reduced to 33% at six months and to 30% at 12 months follow-up. Moreover, patients with T2DM had an odds ratio of 9.5 (95% CI = 3.0–29.7; p < 0.001) for magnesium deficiency when compared to patients without T2DM. Further research into the role of Mg and its role in T2DM and other obesity-related comorbidities are needed. Full article

Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m²), urinary taurine excretion (533 (210–946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (β = 0.126; P = 0.001). During median follow-up for 5.3 (4.5–6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67–0.82); P < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation. Full article

Carotenoids can be metabolized to various apo-carotenoids and retinoids. Apo-15´-carotenoic acid (retinoic acid, RA) is a potent activator of the retinoic acid receptor (RAR) in its all-trans- (ATRA) and 9-cis- (9CRA) forms. In this study we show firstly, that apo-14´-carotenoic acid (A14CA), besides retinoic acids, is present endogenously and with increased levels in the human organism after carrot juice supplementation rich in β-carotene. All-trans-A14C (ATA14CA) is just a moderate activator of RAR-transactivation in reporter cell lines but can potently activate retinoic acid response element (RARE)-mediated signalling in DR5/RARE-reporter mice and potently increase retinoid-reporter target gene expression in ATA14CA-supplemented mice and treated MM6 cells. Further metabolism to all-trans-13,14-dihydroretinoic acid (ATDHRA) may be the key for its potent effects on retinoid target gene activation in ATA14CA-treated MM6 cells and in liver of supplemented mice. We conclude that besides RAs, there are alternative ways to activate RAR-response pathways in the mammalian organism. ATA14CA alone and in combination with its metabolite ATDHRA may be an alternative pathway for potent RAR-mediated signalling. Full article

Vitamin K is crucial for many physiological processes such as coagulation, energy metabolism, and arterial calcification prevention due to its involvement in the activation of several vitamin K-dependent proteins. During this activation, vitamin K is converted into vitamin K epoxide, which must be re-reduced by the VKORC1 enzyme. Various VKORC1 mutations have been described in humans. While these mutations have been widely associated with anticoagulant resistance, their association with a modification of vitamin K status due to a modification of the enzyme efficiency has never been considered. Using animal models with different Vkorc1 mutations receiving a standard diet or a menadione-deficient diet, we investigated this association by measuring different markers of the vitamin K status. Each mutation dramatically affected vitamin K recycling efficiency. This decrease in recycling was associated with a significant alteration of the vitamin K status, even when animals were fed a menadione-enriched diet suggesting a loss of vitamin K from the cycle due to the presence of the Vkorc1 mutation. This change in vitamin K status resulted in clinical modifications in mutated rats only when animals receive a limited vitamin K intake totally consistent with the capacity of each strain to recycle vitamin K. Full article

This cross-sectional study determined whether 6-n-propylthiouracil (PROP) taster status moderates the relationship between food consumption patterns and body composition in children. Children were recruited (n = 342, 50% female, 8–10 y) from across New Zealand. Using a food frequency questionnaire, these food consumption patterns were derived: Processed Foods, Fruit and Vegetables, and Breakfast Foods. Body composition variables included: body fat (%), fat mass (kg), fat mass index (FMI, kg/m²), body mass index (kg/m²) and waist to height ratio (W:Ht). Following adjustment for confounders, Processed Foods were positively associated with %fat (p = 0.015), fat mass (p = 0.004) and FMI (p = 0.016). Taste test strips determined PROP status. For Breakfast Foods, there were small negative associations with all body composition variables (p ≤ 0.001 to 0.037). The population sample was also stratified by PROP taster status. For the non-tasters, there were small to moderate negative associations between Breakfast Foods and each body composition variable (p = 0.003–0.045) except W:Ht (p = 0.112), and these relationships were stronger for girls compared to boys. For the tasters, there were small to moderate positive associations between Processed Foods with %fat (p = 0.030), fat mass (p ≤ 0.001) and FMI (p = 0.014). In conclusion, sensitivity to bitterness may moderate the relationship between food consumption patterns and body composition in children. Full article

Background: Although the anticancer activity of Korean Red Ginseng (KRG) has been known in various cancers, the mechanism of KRG-induced apoptosis is unknown in colorectal cancer (CRC). In our study, we examined whether KRG induces apoptosis in CRC cells. Methods: In the cell viability assay, the concentration of the appropriate KRG extracts was fixed at 2.5 mg/mL in numerous CRC cells. This fixed concentration was in other experiments, and it was confirmed that the KRG extracts induce apoptosis in CRC cells. Results: We found that KRG induced Noxa activation and apoptosis and increased endoplasmic reticulum stress via reactive oxygen species production. This indicated that KRG efficiently enhanced cell death in CRC cells. Conclusion: Our results show that KRG can be used as a possible anticancer drug for patients with CRC Full article

Associations between whole blood transcriptome and clinical phenotypes in vitamin D-deficient overweight and obese children can provide insight into the biological effects of vitamin D and obesity. We determined differentially expressed genes (DEGs) in relation to body mass index (BMI) in vitamin D-deficient black children with a BMI ≥ 85th percentile and ascertained the cardiometabolic phenotypes associated with the DEGs. We examined whole-blood transcriptome gene expression by RNA sequencing and cardiometabolic profiling in 41, 10- to 18-year-old children. We found 296 DEGs in association with BMI after adjusting for age, race, sex, and pubertal status. Cardiometabolic phenotypes associated with the BMI-related DEGs, after adjusting for age, sex, pubertal status, and %total body fat, were (i) flow-mediated dilation (marker of endothelial function), (ii) c-reactive protein (marker of inflammation), and (iii) leptin (adipocytokine). Canonical pathways of relevance for childhood obesity and its phenotypes that were significantly associated with the BMI-related DEGs affected immune cell function/inflammation, vascular health, metabolic function, and cell survival/death; several immune and inflammatory pathways overlapped across the three phenotypes. We have identified transcriptome-based biomarkers associated with BMI in vitamin D-deficient, overweight and obese black children. Modulating effects of vitamin D supplementation on these biomarkers and their related phenotypes need further exploration. Full article

Sodium restriction may potentially reduce iodine intake. This study aimed to determine the effect of sodium restriction (dietary counseling) on 24-h urinary iodine excretion. Diuretics provide an alternative to sodium restriction and are frequently added to sodium restriction, so the effects of hydrochlorothiazide (50 mg daily) and combined therapy were also studied. We performed a post-hoc analysis of a Dutch multi-center, randomized cross-over trial in 45 patients with diabetic kidney disease with a mean age of 65 ± 9 years, mean eGFR of 65 ± 27 mL/min/1.73 m², median albuminuria of 648 [230–2008] mg/24 h and 84% were male. During regular sodium intake with placebo, mean 24 h urinary sodium and iodine excretion were 224 ± 76 mmol/24 h and 252 ± 94 ug/24 h, respectively (r = 0.52, p < 0.001). Mean iodine excretion did not change significantly if sodium restriction and hydrochlorothiazide were applied separately; mean difference −8 ug/day (95% CI −38, 22; p = 0.6) and 14 ug/day (95% CI −24, 52; p = 0.5), respectively. Combined therapy induced a significant decrease in mean iodine excretion (−37 ug/day; 95% CI −67, −7; p = 0.02), yet this was not seen to a clinically meaningful level. The number of patients with an estimated intake below recommended daily allowances did not differ significantly between the four treatment periods (p = 0.3). These findings show that sodium restriction is not a risk factor for iodine deficiency. Full article

Nowadays, obesity and its complications are heavy burdens to western civilization. Surgical procedures remain one of the available therapies for obesity and obesity-associated diseases treatment. Among them, sleeve gastrectomy is the most common bariatric procedure. Despite the well-established fact that sleeve gastrectomy results in significant weight loss, some of its other divergent effects still need to be established. To fulfill this knowledge gap, we examined whether sleeve gastrectomy affects lipid metabolism in the plasma and liver of obese rats. We demonstrated that chronic high-fat diet feeding led to an increment in the level of Proprotein Convertase Subtilisin/Kexin (PCSK)—a regulator of plasma cholesterol concentration—in the liver, which was decreased after the gastrectomy. Moreover, we noticed significant increases in both plasma and liver contents of free fatty acids, diacylgycerides and triacylglycerides in the obese animals, with their reduction after the bariatric surgery. In conclusion, we revealed, presumably for the first time, that sleeve gastrectomy affects lipid metabolism in the liver of obese rats. Full article

Research on weight-loss interventions in emerging adulthood is warranted. Therefore, a cognitive-behavioral group treatment (CBT), including development-specific topics for adolescents and young adults with obesity (YOUTH), was developed. In a controlled study, we compared the efficacy of this age-specific CBT group intervention to an age-unspecific CBT group delivered across ages in an inpatient setting. The primary outcome was body mass index standard deviation score (BMI-SDS) over the course of one year; secondary outcomes were health-related and disease-specific quality of life (QoL). 266 participants aged 16 to 21 years (65% females) were randomized. Intention-to-treat (ITT) and per-protocol analyses (PPA) were performed. For both group interventions, we observed significant and clinically relevant improvements in BMI-SDS and QoL over the course of time with small to large effect sizes. Contrary to our hypothesis, the age-specific intervention was not superior to the age-unspecific CBT-approach. Full article