Assessing the Effects of a Perioperative Nutritional Support and Counseling in Gastrointestinal Cancer Patients: A Retrospective Comparative Study with Historical Controls.

The aim of this study was to investigate the effects of perioperative nutritional therapy care in gastrointestinal (esophageal, gastric, gastroesophageal) cancer patients on nutritional status and disease progression (complications, hospitalization, mortality). We considered 62 gastrointestinal cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (August 2017-July 2019). Of these, 42 patients (as intervention group: IG) received pre- and postoperative nutritional support with counseling, while 20 patients (as historical control group CG) received only postoperative nutritional therapy. Several clinical parameters, such as Body Mass Index (BMI), nutritional risk screening (NRS), phase angle, postoperative complications, length of hospital stay, and mortality, were determined. There were significantly fewer patients with gastric cancer/CDH1 gene mutation and more with esophageal cancer in IG (p = 0.001). Significantly more patients received neoadjuvant therapy in IG (p = 0.036). No significant differences were found between the groups regarding BMI, NRS, complications, length of hospital stay, and mortality. However, the comparison of post- and preoperative parameters in IG showed a tendency to lose 1.74 kg of weight (p = 0.046), a decrease in phase angle by 0.59° (p = 0.004), and an increase in NRS of 1.34 points (p < 0.001). Contrary to prior reports, we found no significant effect of perioperative nutritional therapy care in gastrointestinal cancer patients; however, the small cohort size and infrequent standardization in nutritional status may possibly account for the variance. Considering that oncological pathways and metabolic nutritional pathways are interrelated, dividing patients into subgroups to provide a personalized nutritional approach may help in improving their treatment.

Effect of Two Different Dietary Weight Loss Strategies on Risk Factors for Urinary Stone Formation and Cardiometabolic Risk Profile in Overweight Women.

Overweight has been suggested to increase the risk of kidney stone formation. Although weight reduction might affect risk factors for urolithiasis, findings on the impact of different dietary weight loss strategies are limited. This randomized, controlled study evaluated the effect of a conventional energy-restricted modified diet with (MR group) or without meal replacement (C group) on risk factors for stone formation in overweight women without a history of urolithiasis. Of 105 participants, 78 were included into the per-protocol analysis. Anthropometric, clinical, biochemical, and 24 h urinary parameters were collected at baseline and after 12 weeks. Although both dietary interventions resulted in a significant weight reduction, relative weight loss and rate of responders were higher in the MR group. Weight loss improved cardiometabolic risk profile in both groups. Unfortunately, the benefit of decreased GPT activity in the C group was offset by a significant increase in homocysteine and a decline in GFR. While the relative supersaturation of calcium oxalate decreased significantly in both groups, a significant decline in serum uric acid concentration and relative supersaturation of uric acid was observed only in the MR group. Finally, the energy-restricted modified diet with meal replacement showed significant advantages over the energy-restricted modified diet alone.

Impact of an Infant Formula Containing a Novel Fat Blend (Cow's Milk Fat, Fish and Vegetable Oil) and Prebiotics on Stool Fatty Acid Soaps and Erythrocyte Fatty Acid Profiles in Full-Term Healthy Newborns.

INTRODUCTION: Recently, new commercial infant formulas have been composed considering novel fat blends and oligosaccharides to better resemble the fatty acid (FA) composition and stereospecific distribution (e.g., increased amount of ß-palmitate) as well as probiotics content of human breast milk. We hypothesized that these newly composed infant formulas may decrease fecal FA soap excretion and may positively affect erythrocyte FA profiles compared with regular formulas. METHODS: Healthy infants were randomly assigned to receive a high-sn-2-palmitate formula (>25% of the PA is esterified to the sn-2 position of the glycerol backbone, verum: n = 30) or a "standard" formula containing <10% of PA in sn-2 position and no oligosaccharides (control: n = 27); a non-randomized group of breast-fed infants served as control. Anthropometric data of the infants (body weight, recumbent length, and head circumference) were recorded at inclusion (visit 1) and 6 and 12 weeks after onset of intervention (visits 2 and 3). Blood samples for erythrocyte FA analysis (gas chromatography) were taken at visits 1 and 2; stool samples were collected at visit 2. RESULTS: Quantitative formula intake (mL/kg body weight × day) at visit 2 (verum: 155 ± 30, control: 164 ± 30) and visit 3 (verum: 134 ± 26, control: 134 ± 21) was comparable. Six weeks after onset of intervention, stool total FA soaps, palmitate soaps, and total FAs were similar in both formula-fed groups but significantly higher than in breast-fed infants. During the 6-week intervention, erythrocyte palmitate decreased significantly from baseline in all 3 groups with no group differences (verum: 29.20 ± 1.17 to 27.12 ± 0.66, control: 29.88 ± 2.00 to 27.01 ± 0.94, breast-fed: 30.20 ± 0.86 to 26.84 ± 0.98). For selected FAs, significant changes over time in verum and control group were obvious but without formula effects. Some variations in the FA profile of breast-fed infants compared to both verum and control groups were observed. CONCLUSIONS: In contrast to our hypothesis, feeding a newly composed infant formula based on a fat blend with 25% of PA in the sn-2 position of triacylglycerols and supplemented with a prebiotic could not decrease insoluble FA soap excretion compared with a standard product; in this respect, breastfeeding is obviously the best choice. Surprisingly, erythrocyte FA profiles were comparable in formula-fed and breast-fed infants; obvious alterations in FA composition of the respective fat sources and structure did not affect FA incorporation into membranes. Caution should be, however, exercised in drawing robust conclusions in the absence of larger, adequately powered intervention studies.

Coping Strategies Influence Cardiometabolic Risk Factors in Chronic Psychological Stress: A Post Hoc Analysis of A Randomized Pilot Study.

Chronic psychological stress can result in physiological and mental health risks via the activation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal activity and emotion-focused coping strategies. The impact of different stress loads on cardiometabolic risk is poorly understood. This post hoc analysis of a randomized pilot study was conducted on 61 participants (18-65 years of age) with perceived chronic stress. The Perceived Stress Questionnaire (PSQ30), Psychological Neurological Questionnaire (PNF), anthropometric, clinical and blood parameters were assessed. Subjects were assigned to 'high stress' (HS; PSQ30 score: 0.573 ± 0.057) and 'very high stress' (VHS; PSQ30 score: 0.771 ± 0.069) groups based on the PSQ30. Morning salivary cortisol and CRP were elevated in both groups. Visceral adiposity, elevated blood pressure and metabolic syndrome were significantly more frequent in the HS group vs. the VHS group. The fatty liver index (FLI) was higher (p = 0.045), while the PNF score was lower (p < 0.001) in the HS group. The HS group was comprised of more smokers (p = 0.016). Energy intake and physical activity levels were similar in both groups. Thus, high chronic stress was related to visceral adiposity, FLI, elevated blood pressure and metabolic syndrome in the HS group, while very high chronic stress was associated with psychological-neurological symptoms and a lower cardiometabolic risk in the VHS group, probably due to different coping strategies.

Effect of Fat-Soluble Vitamins A, D, E and K on Vitamin Status and Metabolic Profile in Patients with Fat Malabsorption with and without Urolithiasis.

Patients with intestinal fat malabsorption and urolithiasis are particularly at risk of acquiring fat-soluble vitamin deficiencies. The aim of the study was to evaluate the vitamin status and metabolic profile before and after the supplementation of fat-soluble vitamins A, D, E and K (ADEK) in 51 patients with fat malabsorption due to different intestinal diseases both with and without urolithiasis. Anthropometric, clinical, blood and 24-h urinary parameters and dietary intake were assessed at baseline and after ADEK supplementation for two weeks. At baseline, serum aspartate aminotransferase (AST) activity was higher in stone formers (SF; n = 10) than in non-stone formers (NSF; n = 41) but decreased significantly in SF patients after supplementation. Plasma vitamin D and E concentrations increased significantly and to a similar extent in both groups during intervention. While plasma vitamin D concentrations did not differ between the groups, vitamin E concentrations were significantly lower in the SF group than the NSF group before and after ADEK supplementation. Although vitamin D concentration increased significantly in both groups, urinary calcium excretion was not affected by ADEK supplementation. The decline in plasma AST activity in patients with urolithiasis might be attributed to the supplementation of ADEK. Patients with fat malabsorption may benefit from the supplementation of fat-soluble vitamins ADEK.

Effect of alpha-linolenic acid in combination with the flavonol quercetin on markers of cardiovascular disease risk in healthy, non-obese adults: A randomized, double-blinded placebo-controlled crossover trial.

OBJECTIVES: Alpha-linolenic acid (ALA) and quercetin are characteristic compounds in plant-based diets. Cardioprotective effects have been described for both substances, although a possible benefit of combining ALA and quercetin has not, to our knowledge, been evaluated yet. The aim of this study was to investigate the potential independent and additive effects of ALA and quercetin on blood pressure (BP) and lipid and glucose metabolism, as well as on biomarkers of inflammation, oxidative stress, and antioxidant status in healthy, non-obese men and women. Another aim was to examine whether chronic supplementation of supranutritional doses of quercetin would result in an accumulation of plasma quercetin concentration over time. METHODS: In a double-blinded, placebo-controlled crossover trial, healthy volunteers were randomized to receive 3.6 g/d ALA plus 190 mg/d quercetin or placebo for 8 wk. Data from 67 individuals (34 men, 33 women, mean age: 24.6 y) were assessed. RESULTS: Plasma quercetin, tamarixetin, isorhamnetin, and kaempferol increased significantly from baseline to study end with ALA + quercetin but not with ALA + placebo. No significant effect on office systolic BP, mean 24 h ambulatory BP (ABP), or mean daytime ABP was seen in either study group. Both interventions significantly decreased total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B to a similar extent. No effect on high-density lipoprotein cholesterol, apolipoprotein A1, glucose, uric acid, oxidized low-density lipoprotein, C-reactive protein, or lipid-adjusted retinol, α-tocopherol, or ß-carotene was seen in either group. CONCLUSION: Although dietary supplements of 3.6 g/d ALA over an 8-wk period improved lipid profiles in healthy adults, antioxidative and oxidative status, inflammation, and BP remained unchanged. No evidence was seen for an additive or synergistic effect of ALA plus quercetin on markers of cardiovascular disease risk.

Impact of a Specific Amino Acid Composition with Micronutrients on Well-Being in Subjects with Chronic Psychological Stress and Exhaustion Conditions: A Pilot Study.

Chronic work-life stress leads to dysfunction of the hypothalamus⁻pituitary⁻adrenal axis, the autonomic nervous system, and the serotonergic system, with resultant impairment of overall well-being. Aim of the study was to improve perceived stress by a specific amino acid composition with micronutrients in the verum versus placebo group. A total of 59 participants (18⁻65 years) with self-reported perceived chronic stress and exhaustion conditions participated in this randomized, double-blind, placebo-controlled study. The Perceived Stress Questionnaire (PSQ30), amino acid profile, anthropometric, clinical, blood, urine parameters, and dietary intake were assessed. After 12 weeks, the verum group achieved significantly greater improvements in the total PSQ30 score compared with the placebo group. In the verum group, serum taurine concentration, folic acid concentration, urinary magnesium excretion, and the ratio of l-tryptophan to the sum of competing amino acids rose significantly. In the placebo group, serum concentrations of serotonin, protein, and magnesium decreased significantly, whereas the cardiometabolic risk parameters body weight, body mass index, waist circumference, and waist-to-height ratio increased significantly. Compared with placebo, the verum supplementation resulted in a higher improvement in perceived stress. Beneficial effects on the serotonergic system and preventive effects on magnesium homeostasis and some cardiometabolic risk factors were supposed. Additional effects might be caused by the optimized food intake.

Effects of the flavonol quercetin and α-linolenic acid on n-3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, placebo-controlled, crossover trial.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Mothers' Consumption of Soy Drink But Not Black Tea Increases the Flavonoid Content of Term Breast Milk: A Pilot Randomized, Controlled Intervention Study.

OBJECTIVE: We performed a pilot RCT to prove the hypothesis that a controlled ingestion of polyphenol-rich beverages (soy drink, decaffeinated black tea) in nutritive dosages by nursing women has an effect on the composition (flavonoid concentration, total antioxidant capacity) of breast milk. METHODS: Healthy nursing women were supplemented with either 250 mL of a soy drink (12 mg isoflavones; n = 18), 300 mL decaffeinated black tea (67 mg catechins; n = 18), or 300 mL water (n = 8, control) for 6 days. Milk samples were collected before, during, and after intervention. Flavonoid content (isoflavones/catechins, HPLC) and total antioxidant capacity of milk and test drinks in milk specimens were assessed. RESULTS: Isoflavone content (genistein and daidzein) in breast milk increased up to 12 nmol/L after soy drink consumption; the major flavonoids constituents of black tea (catechin, epicatechin, and respective conjugates) could not be detected in milk samples. With both interventions, the total antioxidant capacity of breast milk was not affected. CONCLUSIONS: Mothers' daily consumption of a soy drink considerably increases isoflavone content of breast milk resulting in an estimated daily exposure of 9.6 nmol isoflavones in a 4-month-old suckling infant. Luminal flavanol uptake from black tea consumed by the nursing mother may be too low to affect flavanol concentrations in breast milk.

Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults with hypertension: a randomized, double-blind, placebo-controlled, crossover trial.

PURPOSE: To determine whether postprandial metabolic and vascular responses induced by a high-fat and high-carbohydrate meal are attenuated by ingestion of the flavonol quercetin. METHODS: Twenty-two overweight-to-obese hypertensive patients participated in a randomized, double-blind, controlled, crossover meal study. They consumed a test meal (challenge) rich in energy (4754 kJ), fat (61.6 g), saturated fatty acids (53 % of total fatty acids), and carbohydrates (113.3 g) with either placebo or 54 mg quercetin. Blood pressure, reactive hyperemia index (RHI), high-sensitive C-reactive protein (hs-CRP), soluble endothelial-derived adhesion molecules, parameters of lipid and glucose metabolism, and markers of antioxidant status were measured before the meal and at 2 and 4 h postprandially. RESULTS: Systolic and diastolic blood pressure increased significantly over time, but were not affected by treatment (placebo or quercetin). During both treatments, serum endothelin-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and plasma asymmetric dimethylarginine slightly decreased over time, whereas RHI increased. Serum triglycerides, total cholesterol, and insulin significantly increased, whereas HDL cholesterol and glucose significantly decreased over time, again with no effect of treatment. Plasma α-tocopherol significantly increased, and plasma Trolox equivalent antioxidative capacity decreased over time. Serum hs-CRP, plasma retinol, and ß-carotene did not significantly change during the trial. CONCLUSION: In hypertensive patients, a high-energy meal did not lead to postprandial impairment of vascular endothelial function. Postprandial metabolic responses induced by the challenge, such as lipemia and insulinemia, were not attenuated by the concomitant ingestion of quercetin. CLINICAL TRIAL: This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00000555.

No effects of quercetin from onion skin extract on serum leptin and adiponectin concentrations in overweight-to-obese patients with (pre-)hypertension: a randomized double-blinded, placebo-controlled crossover trial.

PURPOSE: Chronic low-level systemic and adipose tissue inflammation has been identified as a major etiologic factor in many chronic diseases, including hypertension and cardiovascular diseases. Evidence from experimental studies suggests anti-inflammatory effects of dietary flavonols such as quercetin. METHODS: We investigated the effects of regular intake of quercetin on leptin, adiponectin, biomarkers of inflammation, glucose and insulin in overweight-to-obese patients with pre- and stage 1 hypertension. Another objective was to assess the safety of daily quercetin supplementation measured by parameters of liver and kidney function and of hematology. Subjects (n = 70) were randomized to receive a supra-nutritional dose of 162 mg/d quercetin or placebo in a double-blinded, placebo-controlled crossover trial with 6-week treatment periods separated by a 6-week washout period. Two subjects dropped out for personal reasons. Only data from the remaining 68 subjects were included in the analysis. RESULTS: Compared to placebo, quercetin did not significantly affect serum concentrations of leptin and adiponectin, HOMA-AD or the ratios of leptin/adiponectin and adiponectin/leptin. Neither quercetin nor placebo significantly changed serum C-reactive protein and plasma tumor necrosis factor alpha. Compared to placebo, quercetin did not significantly affect glucose, insulin, HOMA-IR, blood biomarkers of liver and renal function, hematology and serum electrolytes. CONCLUSION: A supra-nutritional dose of 162 mg/d quercetin from onion skin extract for 6 weeks is safe but without significant effects on parameters of systemic and adipose tissue inflammation as well as glucose and insulin in overweight-to-obese subjects with (pre-)hypertension. This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00000555.

Oral High-Dose Vitamin D Dissolved in Oil Raised Serum 25-Hydroxy-Vitamin D to Physiological Levels in Obese Patients After Sleeve Gastrectomy-A Double-Blind, Randomized, and Placebo-Controlled Trial.

BACKGROUND: Osteomalacia and cardiometabolic disorders are favored in morbidly obese patients due to an inadequate vitamin D (VD) status. Former trials supplementing orally VD (20-50 µg/day) in crystalline form after sleeve gastrectomy (SG) could not stabilize serum 25-hydroxycholecalciferol levels at predefined concentrations (≥50 nmol/l). We hypothesized that VD in an oily suspension would increase its bioavailability resulting in normal serum VD levels minimizing markers of cardiometabolic risk. METHODS: Morbidly obese patients (n = 94, BMI 51.8 ± 11.5 kg/m(2)) received orally 80 µg/day VD3 dissolved in oil or placebo (pure oil) in a randomized, double-blind, parallel-group study for 12 weeks after SG. 25-hydroxycholecalciferol, parathyroid hormone, albumin, alkaline phosphatase, phosphate, magnesium, calcium, creatinine, C-reactive protein, lipids, glucose, and glycated hemoglobin were determined in serum/plasma before surgery and after 4 and 12 weeks of supplementation. Intake of energy, fat, and VD were monitored using a 3-day food record. RESULTS: Seventy-nine patients were included in statistical analysis. Preoperatively, 77.2 and 40.5 % presented 25-hydroxycholecalciferol levels <75 and <50 nmol/l, respectively. After 12 weeks of supplementation, significantly more patients in the VD group exhibited levels >50 nmol/l (92 %) and >75 nmol/l (68 %) compared to the placebo group (54 and 22 %, respectively). Parameters of mineral metabolism and cardiometabolic risk were not modulated by intervention. CONCLUSION: Supplementation of 80 µg/day VD3 by oil is an effective and safe measure to prevent VD deficiency and to treat a preexisting undersupply in patients after SG. Cardiometabolic risk factors were, however, not affected; probably, higher VD doses might be necessary. CLINICAL TRIAL REGISTRATION: This trial was registered retrospectively on November 14, 2014, at the German Clinical Trials Register as DRKS00007143.

Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial.

The polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n 70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 6-week washout period. Before and after the intervention, ambulatory blood pressure (ABP) and office BP were measured; urine and blood samples were collected; and endothelial function was measured by EndoPAT technology. In the total group, quercetin did not significantly affect 24 h ABP parameters and office BP. In the subgroup of hypertensives, quercetin decreased 24 h systolic BP by -3·6 mmHg (P=0·022) when compared with placebo (mean treatment difference, -3·9 mmHg; P=0·049). In addition, quercetin significantly decreased day-time and night-time systolic BP in hypertensives, but without a significant effect in inter-group comparison. In the total group and also in the subgroup of hypertensives, vasoactive biomarkers including endothelin-1, soluble endothelial-derived adhesion molecules, asymmetric dimethylarginine, angiotensin-converting enzyme activity, endothelial function, parameters of oxidation, inflammation, lipid and glucose metabolism were not affected by quercetin. In conclusion, supplementation with 162 mg/d quercetin from onion skin extract lowers ABP in patients with hypertension, suggesting a cardioprotective effect of quercetin. The mechanisms responsible for the BP-lowering effect remain unclear.

Elevated hepcidin serum level in response to inflammatory and iron signals in exercising athletes is independent of moderate supplementation with vitamin C and E.

Iron deficiency among endurance athletes is of major concern for coaches, physicians, and nutritionists. Recently, it has been observed that hepcidin, the master regulator of iron metabolism, was upregulated after exercise and was found to be related to interleukin-6 (IL-6) elevation. In this study performed on noniron deficient and well-trained runners, we observed that hepcidin concentrations remain elevated in response to inflammatory and iron signals despite a 28-days supplementation period with vitamins C (500 mg/day) and E (400 IU/day).

Placebo-controlled dietary intervention of stress-induced neurovegetative disorders with a specific amino acid composition: a pilot-study.

BACKGROUND: Psychosocial stress leads to altered neuroendocrine functions, such as serotonergic dysfunction, as well as alterations of the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA)-axis activity resulting in an imbalance between inhibitory and excitatory neurotransmitters. Poor dietary intake of L-tryptophan as a precursor of serotonin increases sensitivity to stress. METHODS: This randomized, double-blind, placebo-controlled study investigated the effect of a specific amino acid composition with micronutrients on neurovegetative disorders and the cardiometabolic risk profile in psychosocially stressed patients. 32 patients (18-65 years) were eligible for protocol analysis. Points in the Psychological Neurological Questionnaire (PNF), clinical and blood parameter, in particular the serotonin level, salivary cortisol levels, and dietary intake were evaluated at baseline and 12 weeks after supplementation. RESULTS: The intervention in the form of either verum or placebo resulted in both groups in a significant decrease of neurovegetative symptoms. However, patients of the placebo group achieved significantly less points in the PNF compared to the verum group. But the rate of responders (≥10 points loss in PNF) was not significantly different between the groups. The macronutrient intake did not differ between verum and placebo group. On average, the HPA-axis was not disturbed in both groups. Blood serotonin indicated in both groups no significant correlation with dietary tryptophan intake or PNF. CONCLUSIONS: Daily supplementation of a specific amino acid composition with micronutrients in psychologically stressed patients resulted in no improvement of neurovegetative disorders as measured by the PNF when compared to the placebo group. TRIAL REGISTRATION: Clinical Trials.gov ( NCT01425983 ).

Is glutamine deficiency the link between inflammation, malnutrition, and fatigue in cancer patients?

PURPOSE: Evaluation of potential associations between plasma glutamine levels and the incidence of cancer related fatigue, physical performance, poor nutritional status, and inflammation in patients with solid tumors. STUDY DESIGN: Mono-center cross-sectional study recruiting 100 (34 women) consecutive patients (September 2009-March 2011; ≥18 y) with solid tumors and causal tumor therapy. METHODOLOGY: Fasting venous blood was harvested for routine clinical chemistry, amino acid (HPLC) and inflammation marker analyses. Clinical assessments included global, physical, affective and cognitive fatigue (questionnaire) and Karnofsky performance status. Nutritional status was evaluated using bioelectrical impedance analysis, the Prognostic Inflammatory and Nutritional Index and plasma protein levels. Regression analyses were performed to correlate continuous variables with plasma glutamine (95% confidence intervals). RESULTS: Nutritional status was impaired in 19% of the patients. Average plasma glutamine concentration (574.0 ± 189.6 µmol/L) was within normal range but decreased with impaired physical function. Plasma glutamine was linked to the ratio extracellular to body cell mass (p < 0.044), CRP (p < 0.001), physical (p = 0.014), affective (p = 0.041), and global fatigue (p = 0.030). Markers of inflammation increased with low physical performance. CONCLUSIONS: The data support our working hypothesis that in cancer patients systemic inflammation maintains a catabolic situation leading to malnutrition symptoms and glutamine deprivation, the latter being associated with cancer related fatigue.

Protein is an important component of nutritional support predicting complications in malnourished hospitalised patients - Details of our previous randomised controlled trial (RCT).

BACKGROUND AND AIMS: Nutritional support can be an effective tool to avoid and reduce malnutrition. However, it is unclear which component, i.e. nutrient, is most efficient. With the present analysis we define the most important predictors of the body weight change and the complication incidence during hospitalisation. METHODS: Data of our previous randomised controlled nutritional trail was analysed according to per-protocol. A factor analysis was performed using binary logistic and multiple linear regression analyses with the outcome variables "complication yes/no" and "body weight change", respectively. RESULTS: Repeated measure ANOVA revealed a highly significant intervention effect for both protein and caloric intake (p < 0.001) after 5 and 10 days of intervention. Patients of the intervention group (IG; n = 59) were able to keep their body weight in contrast to control group (CG; n = 59) patients (68.3 (15.5) kg vs. 64.4 (15.8) kg, p = 0.003). The mean plasma ascorbic acid level was higher in IG than in CG at discharge (47.2 (26.8) µmol/l vs. 34.1 (24.2) µmol/l, p = 0.005). The number of patients suffering from in-hospital complications was lower in IG than in CG (4/59 vs. 13/59, p = 0.034). Positive effects on the antibiotic therapies for infectious complications (1/58 vs. 8/59, p = 0.032), the SF-36 physical summary scale (37 (11) % vs. 33 (9), p = 0.039) and the readmission rates (26/54 vs. 43/58, p = 0.019) were recorded. The mean protein intake predicted the chance of having a complication whereas the body weight change was best predicted by the mean caloric intake. CONCLUSIONS: Caloric and protein intake are important predictors of complications and the change in body weight, respectively. In contrast, age and disease severity did not influence the outcome in our nutritional trial.

Determinants of urolithiasis in patients with intestinal fat malabsorption.

OBJECTIVE: To investigate the determinants of urinary stone formation in patients with fat malabsorption, because, although the prevalence of urolithiasis is greater in patients with intestinal diseases, the pathogenetic mechanisms and risk factors associated with urolithiasis in this population remain partially unsolved. MATERIALS AND METHODS: The present study retrospectively analyzed the determinants of urolithiasis in 51 patients with fat malabsorption due to different intestinal diseases. Anthropometric, clinical, blood, 24-hour urinary parameters, and dietary intake were assessed. RESULTS: The resection rate (ie, pancreatic and/or bowel resection) differed significantly between stone formers (SF; n=10) and nonstone formers (NSF; n=41; 70% vs 29%; P=.027). Urinary citrate was lower (1.606±1.824 vs 3.156±1.968 mmol/24 h; P=.027), while oxalate excretion (0.659±0.292 vs 0.378±0.168 mmol/24 h; P=.002) and the relative supersaturation of calcium oxalate were greater in SF than NSF (8.16±4.61 vs 3.94±2.93; P=.003). Total cholesterol and low-density lipoprotein cholesterol, but also high-density lipoprotein cholesterol, plasma ß-carotene, and vitamin E concentrations, were significantly diminished, whereas serum aspartate aminotransferase activity was significantly greater in SF compared with NSF. Binary logistic regression analysis revealed resection status as a major extrarenal risk factor for stone formation (odds ratio 5.639). CONCLUSION: Increased urinary oxalate and decreased citrate excretion, probably resulting from pancreatic and/or bowel resection with mainly preserved colon, were identified as the most crucial urinary risk factors for stone formation in patients with fat malabsorption. The findings suggest that hyperoxaluria predominantly results from increased colonic permeability for oxalate due to disturbed bile acid metabolism. The impaired status of fat-soluble antioxidants ß-carotene and vitamin E indicates severe malabsorptive states associated with an enhanced stone-forming propensity.

Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea.

L-Theanine, an amino acid in green tea, is suggested to improve cognition and mood. Therefore, L-theanine is available as a supplement and is now used as an ingredient in functional drinks. Because data on the metabolic fate of L-theanine from human studies are lacking, we investigated the kinetics of L-theanine uptake and its metabolites, ethylamine and glutamic acid, in healthy participants. Within a randomized crossover study, 12 participants ingested a bolus of 100 mg L-theanine via capsules or green tea. On further occasions, 3 participants received 50 and 200 mg L-theanine via capsules. Blood and urine were collected before and up to 24 h postconsumption to determine the concentrations of L-theanine, proteinogenic amino acids, and ethylamine in plasma, erythrocytes, and urine by HPLC. L-Theanine increased in plasma, erythrocytes, and urine with comparable results after both treatments. The maximum plasma concentration of L-theanine occurred 0.8 h after intake of 100 mg L-theanine via capsules (24.3 ± 5.7 µmol/L) and tea (26.5 ± 5.2 µmol/L), respectively. The AUC of L-theanine in plasma increased dose dependently after intake of 50, 100, and 200 mg L-theanine via capsules. Moreover, ethylamine and glutamic acid increased in plasma and were excreted by urine after intake of capsules and tea. In conclusion, L-theanine is rapidly absorbed and seems to be hydrolyzed to ethylamine and glutamic acid. A minor part of L-theanine is retained in erythrocytes. Kinetics and urinary excretion of L-theanine, ethylamine, and glutamic acid are comparable after both treatments. Thus, functional effects of L-theanine intake may result from L-theanine, ethylamine, or glutamic acid.

Intravenous free and dipeptide-bound glutamine maintains intestinal microcirculation in experimental endotoxemia.

OBJECTIVE: The administration of glutamine (Gln), which is depleted in critical illness, is associated with an improvement of gut metabolism, structure, and function. The aim of the present study was to evaluate the effects of intravenous Gln and its galenic formulation, l-alanyl-l-glutamine dipeptide (AlaGln), on the intestinal microcirculation during experimental endotoxemia using intravital fluorescence microscopy. Gln or AlaGln administration was performed as pretreatment or post-treatment, respectively. To identify further the underlying mechanisms, amino acid levels were studied. METHODS: Sixty male Lewis rats were randomly divided into six groups (n = 10/group): control, LPS (lipopolysaccharide 5 mg/kg intravenously), Gln/LPS (LPS animals pretreated with Gln 0.75 g/kg Gln intravenously), AlaGln/LPS (LPS animals pretreated with AlaGln intravenously, 0.75 g/kg Gln content), LPS/Gln (LPS animals post-treated with Gln 0.75 g/kg intravenously), and LPS/AlaGln (LPS animals post-treated with AlaGln intravenously, 0.75 g/kg Gln content). Two hours after the endotoxin challenge, the microcirculation of the terminal ileum was studied using intravital fluorescence microscopy. Blood samples were drawn at the beginning, during, and the end of the experiment to determine the amino acid levels. RESULTS: The Gln and AlaGln pre- and post-treatment, respectively, prevented the LPS-induced decrease in the functional capillary density of the intestinal muscular and mucosal layers (P < 0.05). The number of adherent leukocytes in the submucosal venules was significantly attenuated after the Gln and AlaGln pre- and post-treatment (P < 0.05). CONCLUSION: The Gln and AlaGln administrations improved the intestinal microcirculation by increasing the functional capillary density of the intestinal wall and decreasing the submucosal leukocyte activation.