Effects of antioxidant supplementation on bone mineral density, bone mineral content and bone structure in healthy men during 60 days of 6° head-down tilt bed rest: Results from a randomised controlled trial.

Dietary countermeasures to mitigate detrimental spaceflight-induced effects on bone health would alleviate the requirements and the consequences imposed by other types of countermeasures for this risk. We hypothesised that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR), an analogue of spaceflight, would have a protective effect on bone mineral density (BMD), content (BMC) and bone structure parameters. An exploratory, randomised, controlled, single-blind intervention trial was conducted in a parallel design with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study included 14 days of baseline data collection (BDC) before bed rest, followed by 60 days of HDBR and a 14-day recovery period. Ten subjects in the antioxidant group received a supplement (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E and 80 µg/d selenium) daily. Ten subjects in the control group received no supplement. The diet was consistent with dietary reference intakes, individually tailored based on the subject's bodyweight and strictly controlled. We measured whole-body, lumbar spine and femur BMD and BMC, as well as BMD of the cortical and trabecular compartments of the distal radius and tibia, and cortical and trabecular thickness during BDC, HDBR and recovery. Data were analysed using linear mixed models. The supplementation of an antioxidant cocktail did not mitigate the deteriorating effects of HDBR on BMD, BMC and bone structure parameters. Our findings do not support a recommendation for antioxidant supplementation for astronauts.

Is the amino acid pattern in medical nutrition therapy crucial for successfully attenuating muscle mass loss in adult ICU patients? Secondary analysis of a RCT.

BACKGROUND AND AIMS: We hypothesized that in long-term immobilized intensive care unit (ICU) patients, both the quantity and quality of protein nutrition are vital in supporting muscle mass maintenance. Hence, the aim of this secondary analysis of our recently performed RCT was to calculate the intake of individual amino acids and to evaluate the potential associations of amino acid patterns with muscle mass loss during the ICU stay. METHODS: Clinical and nutritional data were collected from a recent RCT conducted in long-term immobilized, critically ill patients receiving medical nutrition therapy with either 1.8 g (interventional group) or 1.2 g (standard group) of protein/amino acids per kg body weight per day over 4 weeks. Intake of the individual amino acids as well as the sum scores of the indispensable, conditionally indispensable, and dispensable amino acids were calculated for all patients, both group specific (n = 21 in each group) and in total (n = 42), based on the detailed nutrition protocols; inter-group differences were analyzed by t-tests. Linear regression models were used to test the effects of individual amino acids and the sum scores on the extent of skeletal muscle loss by measuring the quadriceps muscle layer thickness during the study period. The significance level was adjusted for multiple testing according to the Bonferroni procedure (α = 0.002). RESULTS: In both groups, the proportion of indispensable amino acids was approximately 41% of the total exogenous protein supply, with the proportion of enteral administration slightly over 50%. The intake of conditionally indispensable amino acids (glutamine, tyrosine, cysteine, histidine, and arginine) accounted for 17% and 18% of the total amino acids in the interventional and standard groups, respectively; glutamine (5% of total amino acids) was exclusively administered enterally. The intake of dispensable amino acid varied widely, with glutamic acid, proline, and asparagine/aspartic acid representing the highest proportions (10%, 8%, and 8% of total amino acids, respectively). For all amino acids, no statistically significant association was observed between the quantitative intake and the skeletal muscle changes after terminating the intervention phase. CONCLUSION: This secondary analysis of the RCT conducted in routine clinical practice did not support our working hypothesis that the amino acid patterns of medical nutrition therapy have a statistically significant impact on the skeletal muscle loss in long-term immobilized ICU patients. Due to the limited variety of enteral/parenteral products used in this single-center study, the calculated amino acid patterns showed only small differences. Larger multi-center trials with adequate power are needed to evaluate the potential effects of the individual amino acids or defined amino acid patterns on the muscle protein metabolism in further detail. TRIAL REGISTRATION: German Clinical Trials Register (http://www.drks.de); DRKS-ID: DRKS00013594.

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.

Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial.

BACKGROUND: Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. OBJECTIVES: We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. METHODS: This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 µg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. RESULTS: The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum ß-C-telopeptide of type I collagen (ß-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest-related changes were observed. CONCLUSIONS: Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.

Medical high-protein nutrition therapy and loss of muscle mass in adult ICU patients: A randomized controlled trial.

BACKGROUND & AIMS: The degradation of muscle mass and loss of functional proteins due to catabolism are associated with adverse outcomes in critically ill patients. While an adequate supply of protein within a medical nutrition concept is suggested to minimize proteolysis, the specificities on appropriate dosage and timing are still under debate. The current study aimed to evaluate the effect of two different quantities of protein as part of a standardized energetically controlled nutrition therapy for the preservation of muscle mass in the later phase of critical illness. METHODS: A randomized controlled trial was conducted in 42 critically ill patients (age 65 ± 15; 12 females; SAPS 45 ± 11; TISS 20 ± 7; SOFA-score 7 ± 3). The subjects were randomly assigned to either the intervention (1.8 g protein/kg body weight [BW]/d) or standard (1.2 g protein/kg BW/d) group. Nutrient supply via enteral and/or parenteral nutrition was calculated based on the individual energy expenditure measured by indirect calorimetry and target protein content. Quadriceps muscle layer thickness (QMLT) was observed through sonography at inclusion, and during the follow-up period, two and four weeks after inclusion. The measurement points were fixed on two sides at the midpoint and two-thirds between the anterior superior iliac spine and top of the patella. The data were analyzed descriptively wherein chi-squared tests or unpaired two-samle t-tests checked group differences. Daily changes in muscle mass were estimated using a linear mixed model. All data are shown as the mean ± standard deviation (SD). RESULTS: Actual protein intake reached 1.5 ± 0.5 g and 1.0 ± 0.5 g/kg BW/d in the intervention and standard group, respectively. Mean values of all measurements of QMLT at inclusion (day 13 ± 2 after ICU admission) were 13.5 ± 7.4 mm and 13.4 ± 7.1 mm in the intervention and standard group, respectively (P = 0.967). In both the groups, QMLT decreased over time (P < 0.001), while the estimated mean values of daily QMLT changes were -0.15 ± 0.08 mm (intervention) and -0.28 ± 0.08 mm (standard) without significant between-group differences (intervention effect, P = 0.368; time x intervention effect, P = 0.242). Illness scores and clinical outcomes showed no group differences. CONCLUSION: In this single-center trial the increased amounts of protein (1.5 g vs. 1.0 g/kg BW/d) provided through medical nutrition therapy in the late phase of critical illness did not achieve a statistically significant impact on the loss of muscle mass in long-term immobilized ICU patients. Larger multi-center trials are needed to evaluate whether observed numerical differences in muscle mass could be a true finding, and will translate into improved clinical outcomes. TRIAL REGISTRATION: German Clinical Trials Register (http://www.drks.de/), DRKS-ID: DRKS00013594.

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.

Putative Effects of Nutritive Polyphenols on Bone Metabolism In Vivo-Evidence from Human Studies.

For the prevention and treatment of bone loss related diseases, focus has been put on naturally derived substances such as polyphenols. Based on human intervention studies, this review gives an overview of the effects of dietary significant polyphenols (flavonoids, hydroxycinnamic acids, and stilbenes) on bone turnover. Literature research was conducted using PubMed database and articles published between 01/01/2008 and 31/12/2018 were included (last entry: 19/02/2019). Randomized controlled trials using oral polyphenol supplementation, either of isolated polyphenols or polyphenols-rich foods with healthy subjects or study populations with bone disorders were enclosed. Twenty articles fulfilled the inclusion criteria and the average study quality (mean Jadad score: 4.5) was above the pre-defined cut-off of 3.0. Evidence from these studies does not allow an explicit conclusion regarding the effects of dietary important polyphenols on bone mineral density and bone turnover markers. Differences in study population, habitual diet, lifestyle factors, applied polyphenols, used doses, and polyphenol bioavailability complicate the comparison of study outcomes.

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.

A nutritive dose of pure (-)-epicatechin does not beneficially affect increased cardiometabolic risk factors in overweight-to-obese adults-a randomized, placebo-controlled, double-blind crossover study.

Background: Regular cocoa consumption has been shown to reduce blood pressure, improve lipid profiles, and increase insulin sensitivity and flow-mediated dilatation in healthy adults. It is assumed that these effects can be attributed to polyphenolic cocoa ingredients such as flavanols, especially to (-)-epicatechin. Nutritive intervention studies to prove this hypothesis are scarce. Objective: We aimed to evaluate whether regular consumption of 25 mg of pure (-)-epicatechin can affect increased cardiometabolic risk factors [blood pressure, glucose and lipid metabolism, low-density lipoprotein (LDL) oxidation] in overweight-to-obese subjects. Design: Forty-eight overweight or obese nonsmokers [body mass index (kg/m2) ≥25.0, ages 20-65 y] with clear signs of metabolic syndrome (blood pressure ≥130/85 mm Hg, glucose >5.55 mmol/L, or triglycerides >1.69 mmol/L or cholesterol >5.2 mmol/L in fasting blood) and without chronic diseases were included in a randomized, placebo-controlled, double-blind crossover study. Participants ingested daily 25 mg (-)-epicatechin (encapsulated) or placebo for 2-wk in random order (2-wk washout). After an overnight fast, blood pressure was monitored and blood samples were collected before and after both treatments. Anthropometric data were determined at each visit. Dietary intake was assessed by 3-d food records during both treatments and during run-in and washout phase. Results: Supplementation of pure (-)-epicatechin did not significantly affect blood pressure, glucose, insulin, homeostasis model assessment of insulin resistance, triglycerides, or total, LDL, or HDL cholesterol. Oxidized LDL, vitamins C and E, and ß-carotene in plasma were not modulated. Body weight, fat mass, fat distribution, and the intake of energy, nutrients, and (-)-epicatechin from food remained stable throughout the study. Conclusions: Daily intake of 25 mg of pure (-)-epicatechin for 2 wk does not reduce cardiometabolic risk factors in overweight-to-obese adults. Thus, the hypothesis that the cardioprotective effects of regular cocoa consumption are exclusively ascribed to (-)-epicatechin should be reconsidered. The study was registered at the German Clinical Trial Register as DRKS-ID: DRKS00009846.

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.

Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials.

BACKGROUND & AIMS: Early randomised controlled trials (RCTs) testing whether parenteral nutrition regimens that include glutamine dipeptides improves the outcomes of critically ill patients demonstrated convincingly that this regimen associates with reduced mortality, infections, and hospital stays. However, several new RCTs on the same question challenged this. To resolve this controversy, the present meta-analysis was performed. Stringent eligibility criteria were used to select only those RCTs that tested the outcomes of critically ill adult patients without hepatic and/or renal failure who were haemodynamically and metabolically stabilised and who were administered glutamine dipeptide strictly according to current clinical guidelines (via the parenteral route at 0.3-0.5 g/kg/day; max. 30% of the prescribed nitrogen supply) in combination with adequate nutrition. METHODS: The literature research (PubMed, Embase, Cochrane Central Register of Controlled Trials) searched for English and German articles that had been published in peer-review journals (last entry March 31, 2015) and reported the results of RCTs in critically ill adult patients (major surgery, trauma, infection, or organ failure) who received parenteral glutamine dipeptide as part of an isoenergetic and isonitrogenous nutrition therapy. The following data were extracted: infectious complications, lengths of stay (LOS) in the hospital and intensive care unit (ICU), duration of mechanical ventilation, days on inotropic support, and ICU and hospital mortality rates. The selection of and data extraction from studies were performed by two independent reviewers. RESULTS: Fifteen RCTs (16 publications) fulfilled all selection criteria. They involved 842 critically ill patients. None had renal and/or hepatic failure. The average study quality (Jadad score: 3.8 points) was well above the predefined cut-off of 3.0. Common effect estimates indicated that parenteral glutamine dipeptide supplementation significantly reduced infectious complications (relative risk [RR] = 0.70, 95% CI 0.60, 0.83, p < 0.0001), ICU LOS (common mean difference [MD] -1.61 days, 95% CI -3.17, -0.05, p = 0.04), hospital LOS (MD -2.30 days, 95% CI -4.14, -0.45, p = 0.01), and mechanical ventilation duration (MD -1.56 days, 95% CI -2.88, -0.24, p = 0.02). It also lowered the hospital mortality rate by 45% (RR = 0.55, 95% CI 0.32, 0.94, p = 0.03) but had no effect on ICU mortality. Visual inspection of funnel plots did not reveal any potential selective reporting of studies. CONCLUSIONS: This meta-analysis clearly confirms that when critically ill patients are supplemented with parenteral glutamine dipeptide according to clinical guidelines as part of a balanced nutrition regimen, it significantly reduces hospital mortality, infectious complication rates, and hospital LOS. The latter two effects indicate that glutamine dipeptide supplementation also confers economic benefits in this setting. The present analysis indicates the importance of delivering glutamine dipeptides together with adequate parenteral energy and nitrogen so that the administered glutamine serves as precursor in various biosynthetic pathways rather than simply as a fuel.

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.

Higher plasma quercetin levels following oral administration of an onion skin extract compared with pure quercetin dihydrate in humans.

PURPOSE: To investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans. METHODS: In a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21-33 years were administered a single oral supra-nutritional dose of approximately 163 mg quercetin derived from onion skin extract powder (containing 95.3 % of total flavonoids as quercetin aglycone) or quercetin dihydrate (134 mg quercetin aglycone equivalent). Blood samples were collected before and during a 24-h period after quercetin administration. The concentrations of quercetin and its two monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin), and tamarixetin (4'-O-methyl quercetin), were measured using HPLC with fluorescence detection after plasma enzymatic treatment. RESULTS: The systemic availability, determined by comparing the plasma concentration-time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration (C max) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, t max did not differ significantly between the two formulations. The C max values for isorhamnetin and tamarixetin were 3.8 and 4.4 times higher, respectively, after administration of onion skin extract than after pure quercetin dihydrate. The plasma kinetics of quercetin were not significantly different in men and women. CONCLUSION: Quercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.

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.

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.

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.

Glutamine: an obligatory parenteral nutrition substrate in critical care therapy.

Critical illness is characterized by glutamine depletion owing to increased metabolic demand. Glutamine is essential to maintain intestinal integrity and function, sustain immunologic response, and maintain antioxidative balance. Insufficient endogenous availability of glutamine may impair outcome in critically ill patients. Consequently, glutamine has been considered to be a conditionally essential amino acid and a necessary component to complete any parenteral nutrition regimen. Recently, this scientifically sound recommendation has been questioned, primarily based on controversial findings from a large multicentre study published in 2013 that evoked considerable uncertainty among clinicians. The present review was conceived to clarify the most important questions surrounding glutamine supplementation in critical care. This was achieved by addressing the role of glutamine in the pathophysiology of critical illness, summarizing recent clinical studies in patients receiving parenteral nutrition with intravenous glutamine, and describing practical concepts for providing parenteral glutamine in critical care.

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.