Boron Contents of German Mineral and Medicinal Waters and Their Bioavailability in Drosophila melanogaster and Humans.

SCOPE: Boron is a trace element that naturally occurs in soil, making mineral and medicinal water important contributors to overall intake. Thus, in a systematic screening, the mean boron concentrations of 381 German mineral and medicinal waters are determined. METHODS AND RESULTS: Boron concentrations in mineral and medicinal waters are analyzed by inductively coupled mass spectrometry (ICP-MS). Highest boron values find in waters from the southwest of Germany. The boron content of the waters is positively correlated with the concentration of most other analyzed bulk elements, including calcium, potassium, magnesium, and sodium. Mineral waters with either low (7.9 µg L-1 ), medium (113.9 µg L-1 ), or high (2193.3 µg L-1 ) boron content are chosen for boron exposure experiments in fruit flies (Drosophila melanogaster) and humans. In flies, boron-rich mineral water significantly increases boron accumulation, with the accumulation predominantly occurring in the exoskeleton. In humans, serum boron and 24-h urinary boron excretion significantly increase only in response to the intake of boron-rich mineral water. CONCLUSION: Overall, the current data demonstrate that mineral and medicinal waters vary substantially in the content of boron and that boron-rich mineral water can be used to elevate the boron status, both in flies and humans.

Diagnosis of obesity based on body composition-associated health risks-Time for a change in paradigm.

Traditional diagnosis and understanding of the pathophysiology of obesity are based on excessive fat storage due to a chronically positive energy balance characterized by body mass index (BMI). Quantitative and qualitative analysis of lean and adipose tissue compartments by body composition analysis reveals that characterization of obesity as "overfat" does not facilitate a comprehensive understanding of obesity-associated health risk. Instead of being related to fat mass, body composition characteristics underlying BMI-associated prognosis may depend (i) on accelerated growth by a gain in lean mass or fat-free mass (FFM) in children with early BMI rebound or adolescents with early puberty; (ii) on a low muscle mass in aging, associated chronic disease, or severe illness; and (iii) on impaired adipose tissue expandability with respect to cardiometabolic risk. It is therefore time to call the adipocentric paradigm of obesity into question and to avoid the use of BMI and body fat percentage. By contrast, obesity should be seen in face of a limited FFM/muscle mass together with a limited capacity of fat storage.

Pharmacokinetics of vitamin E, γ-oryzanol, and ferulic acid in healthy humans after the ingestion of a rice bran-enriched porridge prepared with water or with milk.

PURPOSE: In this study, we investigated the absorption and excretion kinetics of antioxidant dietary phytochemicals (vitamin E, γ-oryzanol, and ferulic acid) in healthy humans after the ingestion of an oatmeal porridge supplemented with rice bran extract (RBE) prepared with water or with whole milk, and we compared it with the intake of an equivalent dose of the rice bran content, in the form of RBE oil. METHODS: Twelve healthy volunteers (6 men and 6 women) orally ingested RBE oil (2 g) or RBE-enriched porridge (35 g, including 2-g RBE) with water or with milk, in a three-armed, crossover trial. Blood and urine samples were collected at baseline and up to 24 h after intake. Vitamin E (α-, ß-, γ-, and δ-tocopherols and tocotrienols), ferulic acid (FA), and γ-oryzanol (ORY) were quantified by HPLC. RESULTS: The ingestion of RBE-fortified oatmeal porridge and RBE oil significantly increased FA concentrations in plasma, showing faster absorption and higher maximum plasma concentrations after the intake of the porridges, irrespective of the addition of water or milk. At least part of the FA could have been hydrolyzed from ORY. However, plasma vitamin E concentrations did not increase from baseline, and no intact FA esters (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, campesteryl ferulate, and ß-sitosteryl ferulate) were detected in plasma or urine with any of the meal treatments. CONCLUSIONS: Rice bran extract-enriched porridge and, to a lesser extent, RBE oil, provide relevant sources of bioaccessible and bioavailable ferulic acid, and could be further developed into functional foods with health potential.

The Oral Bioavailability of Trans-Resveratrol from a Grapevine-Shoot Extract in Healthy Humans is Significantly Increased by Micellar Solubilization.

SCOPE: Grapevine-shoot extract Vineatrol30 contains abundant resveratrol monomers and oligomers with health-promoting potential. However, the oral bioavailability of these compounds in humans is low (˂1-2%). The aim of this study was to improve the oral bioavailability of resveratrol from vineatrol by micellar solubilization. METHODS AND RESULTS: Twelve healthy volunteers (six women, six men) randomly ingested a single dose of 500 mg vineatrol (30 mg trans-resveratrol, 75 mg trans-ε-viniferin) as native powder or liquid micelles. Plasma and urine were collected at baseline and over 24 h after intake. Resveratrol and viniferin were analyzed by HPLC. The area under the plasma concentration-time curve (AUC) and mean maximum plasma trans-resveratrol concentrations were 5.0-fold and 10.6-fold higher, respectively, after micellar supplementation relative to the native powder. However, no detectable amounts of trans-ε-viniferin were found in either plasma or urine. The transepithelial permeability of trans-resveratrol and trans-ε-viniferin across differentiated Caco-2 monolayers was consistent to the absorbed fractions in vivo. CONCLUSION: The oral bioavailability of trans-resveratrol from the grapevine-shoot extract Vineatrol30 was significantly increased using a liquid micellar formulation, without any treatment-related adverse effects, making it a suitable system for improved supplementation of trans-resveratrol.

Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study.

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognised in vitro digestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to our in vivo results. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining our in vitro and in vivo observations, the effect of the different aggregation forms on human bioavailability was lower than expected.

Dietary patterns associated with magnetic resonance imaging-determined liver fat content in a general population study.

BACKGROUND: The association between diet and fatty liver disease (FLD) has predominantly been analyzed for single nutrients or foods, and findings have been inconsistent. OBJECTIVE: We aimed to compare associations of hypothesis-driven and exploratory dietary pattern scores with liver fat content. DESIGN: Liver fat was measured by using magnetic resonance imaging as liver signal intensity (LSI) in a population-based, cross-sectional study that included 354 individuals. We applied partial least-squares regression to derive an exploratory dietary pattern score that explained variation in both the intake of 38 food groups, which were assessed by using a food-frequency questionnaire, and LSI. The hypothesis-driven score was calculated on the basis of published studies. Multivariable linear or logistic regression was used to investigate associations between dietary pattern scores and LSI or FLD. RESULTS: A higher percentage of LSI variation was explained by the exploratory (12.6%) compared with the hypothesis-driven (2.2%) dietary pattern. Of the 13 most important food groups of the exploratory dietary pattern, intakes of green and black tea, soups, and beer were also individually associated with LSI values. A 1-unit increase in the exploratory dietary pattern score was positively associated with FLD (OR: 1.56; 95% CI: 1.29, 1.88). Furthermore, a 1-unit increase in the hypothesis-driven dietary pattern score, which consisted of alcohol, soft drinks, meat, coffee, and tea, was positively associated with FLD (OR: 1.25; 95% CI: 1.10, 1.43). CONCLUSION: We defined a hypothesis-driven dietary pattern and derived an exploratory dietary pattern, both of which included alcohol, meat (poultry), and tea, associated with liver fat content independent from confounders, which should be explored in prospective studies.

Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules.

The flavonol quercetin, is one of the major flavonoids found in edible plants. The bioavailability of quercetin in humans may be influenced by the food matrix in which it is consumed as well as by its chemical and physical form. The objective of the present study was to investigate the biokinetics of quercetin from quercetin-enriched cereal bars and quercetin powder-filled hard capsules. In a randomised, single-blinded, diet-controlled cross-over study, six healthy women aged 22-28 years took a single oral dose of approximately 130 mg quercetin equivalents from either quercetin-enriched cereal bars (containing 93·3 % quercetin aglycone plus 6·7 % quercetin-4'-glucoside) or quercetin powder-filled hard capsules (100 % quercetin aglycone). Blood samples were drawn before and after quercetin administration over a 24 h period. The concentrations of quercetin and its monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin) and tamarixetin (4'-O-methyl quercetin), were measured by HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability as determined by comparing the plasma concentration-time curves of quercetin was found to be five times and the cmax values six times higher after ingestion of 130 mg quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In contrast, tmax did not differ significantly between the two treatments. The cmax values for isorhamnetin and tamarixetin were four and nine times higher after ingestion of quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In conclusion, quercetin from quercetin-enriched cereal bars is significantly more bioavailable than from quercetin powder-filled hard capsules.

Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study.

Regular consumption of flavonoids may reduce the risk for CVD. However, the effects of individual flavonoids, for example, quercetin, remain unclear. The present study was undertaken to examine the effects of quercetin supplementation on blood pressure, lipid metabolism, markers of oxidative stress, inflammation, and body composition in an at-risk population of ninety-three overweight or obese subjects aged 25-65 years with metabolic syndrome traits. Subjects were randomised to receive 150 mg quercetin/d in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 5-week washout period. Mean fasting plasma quercetin concentrations increased from 71 to 269 nmol/l (P < 0.001) during quercetin treatment. In contrast to placebo, quercetin decreased systolic blood pressure (SBP) by 2.6 mmHg (P < 0.01) in the entire study group, by 2.9 mmHg (P < 0.01) in the subgroup of hypertensive subjects and by 3.7 mmHg (P < 0.001) in the subgroup of younger adults aged 25-50 years. Quercetin decreased serum HDL-cholesterol concentrations (P < 0.001), while total cholesterol, TAG and the LDL:HDL-cholesterol and TAG:HDL-cholesterol ratios were unaltered. Quercetin significantly decreased plasma concentrations of atherogenic oxidised LDL, but did not affect TNF-alpha and C-reactive protein when compared with placebo. Quercetin supplementation had no effects on nutritional status. Blood parameters of liver and kidney function, haematology and serum electrolytes did not reveal any adverse effects of quercetin. In conclusion, quercetin reduced SBP and plasma oxidised LDL concentrations in overweight subjects with a high-CVD risk phenotype. Our findings provide further evidence that quercetin may provide protection against CVD.

Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans.

Our aim was to investigate the effects of an oral supplementation of quercetin at 3 different doses on plasma concentrations of quercetin, parameters of oxidant/antioxidant status, inflammation, and metabolism. To this end, 35 healthy volunteers were randomly assigned to take 50, 100, or 150 mg/d (group Q50-Q150) quercetin for 2 wk. Fasting blood samples were collected at the beginning and end of the supplementation period. Compared with baseline, quercetin supplementation significantly increased plasma concentrations of quercetin by 178% (Q50), 359% (Q100), and 570% (Q150; P < 0.01 for all). High interindividual variation was found for plasma quercetin concentrations (36-57%). Quercetin did not affect concentrations of serum uric acid or plasma alpha- and gamma-tocopherols, oxidized LDL, and tumor necrosis factor-alpha, or plasma antioxidative capacity as assessed by the ferric-reducing antioxidant potential and oxygen radical absorbance capacity assays. In addition, serum lipids and lipoproteins, body composition, and resting energy expenditure did not significantly change during quercetin supplementation. Pharmacokinetics of quercetin were investigated in a subgroup of 15 volunteers. The areas under the plasma concentration-time curves ranged from 76.1 mumol.min.L(-1) to 305.8 mumol.min.L(-1) (50- and 150-mg dosages, respectively). Median maximum plasma concentrations of quercetin (431 nmol/L) were observed 360 min after intake of 150 mg quercetin. In conclusion, daily supplementation of healthy humans with graded concentrations of quercetin for 2 wk dose-dependently increased plasma quercetin concentrations but did not affect antioxidant status, oxidized LDL, inflammation, or metabolism.

Effect of hyperbaric oxygen and vitamin C and E supplementation on biomarkers of oxidative stress in healthy men.

The objectives of the present study were to evaluate the effect of normobaric and hyperbaric O2 (HBO) on plasma antioxidants and biomarkers of oxidative stress in plasma and urine and to investigate the effect of a 4-week vitamin C plus E supplementation on HBO-induced oxidative stress. Nineteen healthy men were exposed to HBO (100 % O2; 240 kPa) before and after 4 weeks' supplementation with 500 mg vitamin C plus 165 mg alpha-tocopherol equivalents. Exposure to 21 % O2 at 100 kPa served as intra-individual controls (control). Samples for the analysis of plasma antioxidants and oxidative stress biomarkers were collected before and immediately after each treatment. The present results showed that when compared with 'control', a single exposure to HBO resulted in a decrease of plasma vitamin C (P = 0.027) and an increase of lipid peroxides (P = 0.0008) and urinary 8-oxo-deoxyguanosine (8-oxodG) excretion (P = 0.006). Oxidative stress was not prevented by a 4-week supplementation with vitamins C and E. HBO-induced changes in plasma parameters correlated with basal antioxidant levels. The increase of urinary 8-oxodG after HBO plus supplementation correlated negatively with vitamin E intake (P = 0.023). We concluded that in healthy men HBO caused oxidative stress, which could not be prevented by dietary vitamin C plus E supplementation. The present data support the idea that HBO is a suitable model for oxidative stress in healthy volunteers.

Influence of vitamin C and E supplementation on oxidative stress induced by hyperbaric oxygen in healthy men.

AIM: To investigate the effect of a 4-week vitamin C and E supplementation on oxidative stress induced by hyperbaric oxygen (HBO). METHODS: 19 healthy men were exposed to 3 sequential protocols, i.e. HBO (100% O2, 2.4 bar, 131 min) before (T1) and after 4 weeks of daily supplementation with 500 mg slow-release vitamin C and 272 IU vitamin E (T2). A normoatmospheric protocol (21% O2, 1.0 bar, 131 min) served as control treatment (nonexposed). Blood samples were taken before (B) and immediately after (A) treatment. Plasma levels of vitamin A, C, E, beta-carotene, reduced glutathione and malondialdehyde were measured by HPLC. Antioxidative capacity and lipid peroxides in plasma were analyzed by ELISA. RESULTS: HBO decreased vitamin C and antioxidative capacity (T1). At T1, Delta A - B of vitamin C and lipid peroxides was different from nonexposed. Vitamin supplementation increased plasma levels of vitamin C and E by 28 and 37%, respectively. Vitamin supplementation led to decreased concentrations of lipid peroxides and reduced glutathione. After supplementation, HBO decreased vitamin C and reduced glutathione. At T2, Delta A - B of vitamin C and lipid peroxides was significantly different from nonexposed. CONCLUSION: In humans, oxidative stress decreased plasma levels of vitamin C and antioxidative capacity and increased plasma lipid peroxides. Supplementation with vitamin C and E did not prevent these effects.

Determinants of hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation.

BACKGROUND: Homocysteine metabolism may be impaired in chronic liver disease, possibly contributing to fibrogenesis and disease complications. OBJECTIVE: The goal was to investigate the prevalence and determinants of basal and postprandial hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation (OLT). DESIGN: This was a cross-sectional study of 323 patients with chronic liver disease (93 with hepatitis, 8 with fatty liver, 168 with cirrhosis, and 54 after OLT) and 25 healthy control subjects. Portohepatovenous gradients of total homocysteine (tHcy) and methionine and postload methionine and tHcy kinetics before and after 10 d of supplementation with folate plus vitamin B-6 were investigated in subgroups. RESULTS: Basal hyperhomocysteinemia was observed in all patient groups (34% of patients with hepatitis, 50% with fatty liver, 54% with cirrhosis, and 52% after OLT). It was more frequently seen in patients with elevated plasma creatinine concentrations and at advanced stages of liver disease. Mean plasma folate was normal in patients with liver disease, but vitamin B-12 was elevated in cirrhosis and vitamin B-6 was low after OLT. There were significant negative associations between tHcy and folic acid or vitamin B-12 concentrations in control subjects and in patients with hepatitis and after OLT. No systematic association between portohepatovenous differences in tHcy and methionine concentrations was found. Cirrhosis was accompanied by impaired methionine clearance. After vitamin supplementation, the area under the tHcy curve improved in cirrhosis at nearly unchanged basal tHcy concentrations. CONCLUSIONS: Basal hyperhomocysteinemia is seen in approximately 50% of patients with cirrhosis and after OLT. Basal tHcy concentrations do not change significantly after supplementation with folate and vitamin B-6, but postprandial Hcy metabolism improves.