Birgit Stoffel-Wagner

Antiepileptic drugs interact with folate and vitamin B12 serum levels

Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12.

S-Adenosylmethionine is decreased in the cerebrospinal fluid of patients with Alzheimer's disease

Background: Increased plasma homocysteine levels have been described as an independent risk factor for Alzheimer’s disease (AD), but the underlying pathophysiology is unclear. Objective: This single-center, cross-sectional, correlational study analyzed homocysteine metabolism in 60 AD patients and 60 control subjects. Methods: Fasting plasma levels of vitamin B12, folate and homocysteine as well as cerebrospinal fluid (CSF) levels of folate derivates, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine were measured. In addition, the apolipoprotein E (APOE) genotype was determined. Results: As expected, the APOE4 allele was significantly overrepresented in AD patients compared with controls (p < 0.001). Homocysteine plasma levels in the highest quartile were more frequent in the AD patients than in the controls (p = 0.008). In addition, AD patients had significantly lower CSF levels of the methyl group donor SAM (193 ± 31 vs. 207 ± 37 nmol/l; p = 0.032). Accordingly, the SAM/SAH ratio, which represents the methylation capacity, was significantly lower in the CSF of the AD patients (7.6 ± 2.4 vs. 9.1 ± 2.8; p = 0.003). Further, explorative analysis of all subjects showed that CSF SAM levels were lower in carriers of the APOE4 allele compared with noncarriers (189 ± 30 vs. 207 ± 36 nmol/l; p = 0.010). Of the individuals with CSF SAM levels in the lowest quartile, 63% carried the APOE4 allele compared with 17% of the individuals with CSF SAM levels in the highest quartile (Pearson: χ2 = 9.9; p = 0.002; odds ratio 0.126, 95% confidence interval 0.32–0.49). Conclusion: These data suggest that AD is associated with lower CSF SAM levels and that this is at least partly due to an association of the APOE4 allele with reduced SAM levels in the CSF.

Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: A PRCT

BACKGROUND & AIMSn: We hypothesize that wound closure in trauma patients with disorders in wound healing is accelerated by supplementation of antioxidant micronutrients and glutamine.nnnMETHODSnIn a randomized, double-blind, placebo-controlled trial, 20 trauma patients with disorders in wound healing were orally supplemented with antioxidant micronutrients (ascorbic acid, α-tocopherol, β-carotene, zinc, selenium) and glutamine (verum) or they received isoenergetic amounts of maltodextrine (placebo) for 14 days. Plasma/serum levels of micronutrients, glutamine, and vascular endothelial growth factor-A (VEGF-A) were determined before and after supplementation. In the wound, several parameters of microcirculation were measured. Time from study entry to wound closure was recorded.nnnRESULTSnMicronutrients in plasma/serum did not change except for selenium which increased in the verum group (1.1 ± 0.2 vs. 1.4 ± 0.2 μmol/l; P = 0.009). Glutamine decreased only in the placebo group (562 ± 68 vs. 526 ± 55 μmol/l; P = 0.047). The prevalence of hypovitaminoses and the concentration of VEGF-A did not change. Considering microcirculation, only O(2)-saturation decreased in the placebo group (56.7 ± 23.4 vs. 44.0 ± 24.0 [arbitrary units]; P = 0.043). Wound closure occurred more rapidly in the verum than in the placebo group (35 ± 22 vs. 70 ± 35 d; P = 0.01).nnnCONCLUSIONSnTime to wound closure can be shortened by oral antioxidant and glutamine containing supplements in trauma patients with disorders in wound healing.

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.

Extracellular micronutrient levels and pro-/antioxidant status in trauma patients with wound healing disorders: results of a cross-sectional study

BackgroundDisorders in wound healing (DWH) are common in trauma patients, the reasons being not completely understood. Inadequate nutritional status may favor DWH, partly by means of oxidative stress. Reliable data, however, are lacking. This study should investigate the status of extracellular micronutrients in patients with DWH within routine setting.MethodsWithin a cross-sectional study, the plasma/serum status of several micronutrients (retinol, ascorbic acid, 25-hydroxycholecalciferol, α-tocopherol, β-carotene, selenium, and zinc) were determined in 44 trauma patients with DWH in addition to selected proteins (albumin, prealbumin, and C-reactive protein; CRP) and markers of pro-/antioxidant balance (antioxidant capacity, peroxides, and malondialdehyde). Values were compared to reference values to calculate the prevalence for biochemical deficiency. Correlations between CRP, albumin and prealbumin, and selected micronutrients were analyzed by Pearson’s test. Statistical significance was set at Pu2009<u20090.05.ResultsMean concentrations of ascorbic acid (23.1u2009±u200915.9xa0μmol/L), 25-hydroxycholecalciferol (46.2±30.6xa0nmol/L), β-carotene (0.6u2009±u20090.4xa0μmol/L), selenium (0.79±0.19xa0μmol/L), and prealbumin (24.8u2009±u20098.2xa0mg/dL) were relatively low. Most patients showed levels of ascorbic acid (<28xa0μmol/L; 64%), 25-hydroxycholecalciferol (<50xa0μmol/L; 59%), selenium (≤ 94xa0μmol/L; 71%) and β-carotene (<0.9xa0μmol/L; 86%) below the reference range. Albumin and prealbumin were in the lower normal range and CRP was mostly above the reference range. Plasma antioxidant capacity was decreased, whereas peroxides and malondialdehyde were increased compared to normal values. Inverse correlations were found between CRP and albumin (Pu2009<u20090.05) and between CRP and prealbumin (Pu2009<u20090.01). Retinol (Pu2009<u20090.001), ascorbic acid (Pu2009<u20090.01), zinc (Pu2009<u20090.001), and selenium (Pu2009<u20090.001) were negatively correlated with CRP.ConclusionsTrauma patients with DWH frequently suffer from protein malnutrition and reduced plasma concentrations of several micronutrients probably due to inflammation, increased requirement, and oxidative burden. Thus, adequate nutritional measures are strongly recommended to trauma patients.

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

PurposeTo investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans.MethodsIn a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21–33xa0years were administered a single oral supra-nutritional dose of approximately 163xa0mg quercetin derived from onion skin extract powder (containing 95.3xa0% of total flavonoids as quercetin aglycone) or quercetin dihydrate (134xa0mg 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.ResultsThe systemic availability, determined by comparing the plasma concentration–time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration (Cmax) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, tmax did not differ significantly between the two formulations. The Cmax 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.ConclusionQuercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.

Preoperative micronutrient status in morbidly obese patients before undergoing bariatric surgery: results of a cross-sectional study

BACKGROUNDnReliable information on micronutrient status before bariatric surgery is needed to optimize preoperative nutritional status and postoperative nutritional therapy.nnnOBJECTIVEnTo investigate the pro-/vitamin and mineral status and its association with nutrient intake in morbidly obese patients seeking bariatric surgerynnnSETTINGnKlinikum Vest, Recklinghausen, Germany.nnnMETHODSnThe cross-sectional study investigated retinol, ascorbic acid, tocopherol, and β-carotene (high-pressure liquid chromatography), 25-hydroxycholecalciferol (enzyme-linked immunosorbent assay), and calcium, phosphate, and magnesium (photometry) in serum/plasma in 43 patients (body mass index: 52.6±10.5 kg/m(2)) before sleeve gastrectomy. Albumin, parathyroid hormone, and alkaline phosphatase were analyzed. Data were compared with accepted cutoff values. Dietary intake was estimated by 3-day food records, and nutrient intake was compared with recommended values.nnnRESULTSnOne third of participants had ascorbic acid concentrations<28 nmol/L. All patients had β-carotene levels≤.9 µmol/L, although retinol was below the cutoff value (<.7 µmol/L) in only 5%. Tocopherol/cholesterol-ratio was always>2.8 µmol/mmol. Of the patients, 84% had 25-hydroxycholecalciferol levels below 50 nmol/L. Parathyroid hormone was elevated in 23% (>6.5 pmol/L). Calcium, magnesium, and alkaline phosphatase were always, and phosphate was mostly (98%) above cutoff values. Intake of retinol (23%), ascorbic acid (55.8%), vitamin D (90.7%), tocopherol (48.8%), and β-carotene (<2.0 mg/d; 37.2%) were often below recommendations. Correlations between serum/plasma concentrations and nutritional intake and associations between low concentrations and inadequate intake were not observed.nnnCONCLUSIONSnMany morbidly obese patients in Germany suffer from deficiencies in multiple micronutrients, particularly vitamin D, ascorbic acid, and β-carotene before sleeve gastrectomy. Measurement of preoperative micronutrient status will help supplement patients before, and optimize nutritional therapy after, surgery.

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

PurposeChronic 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.MethodsWe 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 (nxa0=xa070) were randomized to receive a supra-nutritional dose of 162xa0mg/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.ResultsCompared 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.ConclusionA supra-nutritional dose of 162xa0mg/d quercetin from onion skin extract for 6xa0weeks 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

BackgroundOsteomalacia and cardiometabolic disorders are favored in morbidly obese patients due to an inadequate vitamin D (VD) status. Former trials supplementing orally VD (20–50xa0μg/day) in crystalline form after sleeve gastrectomy (SG) could not stabilize serum 25-hydroxycholecalciferol levels at predefined concentrations (≥50xa0nmol/l). We hypothesized that VD in an oily suspension would increase its bioavailability resulting in normal serum VD levels minimizing markers of cardiometabolic risk.MethodsMorbidly obese patients (nu2009=u200994, BMI 51.8u2009±u200911.5xa0kg/m2) received orally 80xa0μg/day VD3 dissolved in oil or placebo (pure oil) in a randomized, double-blind, parallel-group study for 12xa0weeks 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 12xa0weeks of supplementation. Intake of energy, fat, and VD were monitored using a 3-day food record.ResultsSeventy-nine patients were included in statistical analysis. Preoperatively, 77.2 and 40.5xa0% presented 25-hydroxycholecalciferol levels <75 and <50xa0nmol/l, respectively. After 12xa0weeks of supplementation, significantly more patients in the VD group exhibited levels >50xa0nmol/l (92xa0%) and >75xa0nmol/l (68xa0%) compared to the placebo group (54 and 22xa0%, respectively). Parameters of mineral metabolism and cardiometabolic risk were not modulated by intervention.ConclusionSupplementation of 80xa0μg/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 RegistrationThis trial was registered retrospectively on November 14, 2014, at the German Clinical Trials Register as DRKS00007143.

Need of standardization for creatinine and cystatin C-based GFR equations in renal transplantation

Sir, We read with interest the detailed comparison of various creatinineand cystatin C (Cys C)-based equations to determine GFR in patients after kidney transplantation [1]. This publication provides a comprehensive overview of the most commonly used equations and importantly, applies inulin clearance as gold standard GFR measurement. The authors conclude that creatinine-based formulae are not inferior to Cys C-based estimations of GFR. However, we do have some concerns and would like to draw attention to the fact that neither the creatinine determination calibrated method (e.g. IDMS method) nor the accepted methods for Cys C determination (Dade Behring or DAKO) were used. Although the lack of calibration is discussed as a potential drawback, the consequences of the presented results are not outlined. As demonstrated in a recent publication, even a very small bias from the IDMS-creatinine (+1.15 μmol/l) results in a considerable modification of bias, precision and accuracy [2]. To provide a mathematical example for the MDRD equation, an overestimation of 5 μmol/l, at a creatinine level of 100 μmol/l, leads to an increase in one of the multipliers of the MDRD equation: [105/88.4]−1.154 = 0.82 instead of [100/88.4]−1.154 = 0.867. This means, for a 50-year-old Caucasian male, the MDRD equation will yield 64.8 ml/min/1.73m2 instead of 68.6 ml/min/1.73m2. Surely this is of limited clinical impact; however, it will affect the statistical results of the above-mentioned publication considerably. In regard to the Cys C-based equations, it should be noted that virtually all of the applied equations are based on Dade Behring or DAKO assays which were not applied in this study. Application of a different Cys C determination technique introduces a bias affecting the performance of the Cys C-based estimation. Naturally, even a high correlation of the applied Cys C method with both assays does not exclude a systematic overor underestimation. Thus, a valid conclusion is hampered if non-IDMScalibrated creatinine-based equations are compared with formulae based on non-standardized Cys C. In conclusion, this work is only interesting for transplant centres that determine creatinine by a SYNCHRON LX 20 system and Cys C by ELx808TM absorbance microplates. Outside of these laboratory settings, the presented data are of limited usefulness. Conflict of interest statement. None declared