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ObjectiveTo gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS.DesignWe performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling.ResultsThirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (p<0.001) but not the high FODMAP group. LBTs showed a minor decrease in H2 production in the low FODMAP compared with the high FODMAP group. Metabolic profiling of urine showed groups of patients with IBS differed significantly after the diet (p<0.01), with three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) being primarily responsible for discrimination between the two groups. Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p<0.05). Low FODMAP diet increased Actinobacteria richness and diversity, and high FODMAP diet decreased the relative abundance of bacteria involved in gas consumption.ConclusionsIBS symptoms are linked to FODMAP content and associated with alterations in the metabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms.Trial registration numberNCT01829932.

Dried fruits, like their fresh homologues, contain relatively high concentrations of antioxidants. The aim of this study was to determine the health outcomes of raisin consumption on patients with diabetes. We examined the effects of dried grapes (Vitis vinifera) cultivated in Greece, namely Corinthian Raisins (CR) on blood pressure, fasting glucose, glucated hemoglobin (HbA1c), lipid peroxidation, high-sensitivity C-reactive protein, antioxidant status, and cytokines in patients with type 2 diabetes mellitus (T2DM). Forty-eight well-controlled patients with T2DM from the diabetes outpatient clinic of our hospital were recruited to a two-armed, randomized, controlled, 24-wk prospective intervention trial in order to examine the health outcomes of CR consumption. All participants were reported to consume less fruits and vegetables than the recommended amount of five servings daily. Participants in the intervention were instructed to consume CR equal to two fruit servings (36 g/d), replacing snacks with similar energy density twice during the day. Anthropometric and blood pressure measurements, assessment of dietary intake, and fasting blood draws were conducted at baseline and at week 24. Also, phenolic compounds present in CR were analyzed in plasma of the patients. t Test for parametric data and Mann-Whitney test or Wilcoxon test for non-parametric data were performed. Significance was set at P < 0.05. Body weight, glycemic control, and lipid profile were not affected in either arm. Patients in the CR arm reduced their diastolic blood pressure and increased their total antioxidant potential significantly compared with baseline. The differences between the two groups at week 24 were significant. No change in high-sensitivity C-reactive protein was observed. A significant difference in plasma circulating p-hydroxybenzoic acid was observed between groups at the end of the trial. Our study shows that naturally CR may improve health features in patients with well-controlled T2DM.

Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso -butyl paraben ( iso -BuP) and n -butyl paraben ( n -BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p -hydroxybenzoic acid (PHBA) and p -hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH- n -BuP and 2OH- iso -BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso -BuP represented only 6.8 % and n -BuP 5.6 %. Additionally, for iso -BuP, about 16 % was excreted as 2OH- iso -BuP and for n -BuP about 6 % as 3OH- n -BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2–63.8 %). PHBA represented 3.0–7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5–85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.

Use of personal care products, such as makeup, soaps, and sunscreen, may expose adolescent girls to potential endocrine disruptors, including phthalates, parabens, and other phenols. We evaluated the relationship between recent self-reported personal care product use and concentrations for urinary metabolites of phthalates, parabens, triclosan, and benzophenone-3 (BP-3) in 100 Latina adolescents. Girls who reported using makeup every day vs. rarely/never had higher urinary concentrations of monoethyl phthalate (MEP) (102.2 ng/mL vs. 52.4 ng/mL, P-value: 0.04), methyl paraben (MP) (120.5 ng/mL vs. 13.4 ng/mL, P-value < 0.01), and propyl paraben (PP) (60.4 ng/mL vs. 2.9 ng/mL, P-value < 0.01). Girls who reported recent use of specific makeup products, including foundation, blush, and mascara, had higher urinary concentrations of MEP, mono-n-butyl phthalate (MBP), MP, and PP. Use of Colgate Total toothpaste was associated with 86.7% higher urinary triclosan concentrations. Use of sunscreen was associated with 57.8% higher urinary concentrations of BP-3. Our findings suggest that personal care product use is associated with higher exposure to certain phthalates, parabens, and other phenols in urine. This may be especially relevant in adolescent girls who have high use of personal care products during a period of important reproductive development.

An eco-friendly method for the determination of sweeteners (aspartame, acesulfame-K) and preservatives (benzoic acid, sorbic acid, methylparaben, ethylparaben) in functional beverages and flavoured waters using thin film microextraction (TFME) and high-performance liquid chromatography with UV detection (HPLC-UV) was proposed. A series of fourteen green and renewable solidified natural deep eutectic solvents (NADESs) were prepared and tested as ‘eutectosorbents’ in TFME for the first time. In the proposed method, the NADES containing acetylcholine chloride and 1-docosanol at a 1:3 molar ratio was finally chosen to coat a support. Four factors, i.e., the mass of the NADES, pH of the samples, extraction time, and desorption time, were tested in the central composite design to select the optimal TFME conditions. Limits of detection were equal to 0.022 µg mL−1 for aspartame, 0.020 µg mL−1 for acesulfame-K, 0.018 µg mL−1 for benzoic acid, 0.026 µg mL−1 for sorbic acid, 0.013 µg mL−1 for methylparaben, and 0.011 µg mL−1 for ethylparaben. Satisfactory extraction recoveries between 82% and 96% were achieved with RSDs lower than 6.1% (intra-day) and 7.4% (inter-day). The proposed ‘eutectosorbent’ presented good stability that enabled effective extractions for 16 cycles with recovery of at least 77%. The proposed NADES-TFME/HPLC-UV method is highly sensitive and selective. However, the use of a solid NADES as a sorbent, synthesized without by-products, without the need for purification, and with good stability on a support with the possibility of reusability increases the ecological benefit of this method. The greenness aspect of the method was evaluated using the Complex modified Green Analytical Procedure Index protocol and is equal to 84/100.

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother–child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation. Parabens are preservatives widely used in consumer products including cosmetics and food. Here the authors demonstrate that maternal paraben exposure may contribute to childhood overweight development by an altered neuronal appetite regulation.

Our previous studies showed that populations in China are widely exposed to phthalates and parabens. Nevertheless, sources of Chinese exposure to phthalates and parabens are not well understood. In this study, we measured concentrations of nine phthalates and six parabens in five categories of personal care products (PCPs, N = 52) collected from Tianjin, China, and estimated human exposure doses to these compounds. The most frequently detected phthalates and parabens in PCPs were diethyl phthalate (DEP) (detection frequency 54 %), methyl paraben (MeP), and n-propyl paraben (PrP) (~75 %). The concentrations of DEP in PCPs ranged from not detected (ND; <0.1 μg/g) to 937 μg/g. The highest concentrations of MeP and PrP were 2,826 and 1,564 μg/g, respectively. Median exposure dose to parabens through dermal application of PCPs in China was estimated at 18,700 μg/d, which was two orders of magnitude greater than that calculated for phthalates (45.5 μg/d). Hand and body lotions were the major contributors to exposures, and the daily exposure doses for DEP, MeP, and PrP from these products were 38.4, 10,200 and 4,890 μg, respectively.

Background: Parabens are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Widespread human exposure to parabens has been recently documented, and some parabens have demonstrated adverse effects on male reproduction in animal studies. However, human epidemiologic studies are lacking. Objective: We investigated relationships between urinary concentrations of parabens and markers of male reproductive health in an ongoing reproductive epidemiology study. Methods: Urine samples collected from male partners attending an infertility clinic were analyzed for methyl paraben (MP), propyl paraben (PP), butyl paraben (BP), and bisphenol A (BPA). Associations with serum hormone levels (n = 167), semen quality parameters (n = 190), and sperm DNA damage measures (n = 132) were assessed using multivariable linear regression. Results: Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP. We observed no statistically significant associations between MP or PP and the outcome measures. Categories of urinary BP concentration were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage (p for trend = 0.03). When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage (p for trend = 0.03). Assessment of paraben concentrations measured on repeated urine samples from a subset of the men (n = 78) revealed substantial temporal variability. Conclusions: We found no evidence for a relationship between urinary parabens and hormone levels or semen quality, although intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage warrants further investigation.

Backround: Laboratory and human studies raise concerns about endocrine disruption and asthma from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. Objectives: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. Methods: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. Results: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. Conclusions: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid some target chemicals—synthetic fragrances, BPA, and regulated active ingredients— using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chemicals.

Background: Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Objectives: We assessed exposure to methyl, ethyl, propyl, and butyl parabens in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey. Methods: We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution—high-performance liquid chromatography/tandem mass spectrometry. Results: We detected methyl paraben (MP) and propyl paraben (PP) in 99.1% and 92.7% of the samples, respectively. We detected ethyl (42.4%) and butyl (47%) parabens less frequently and at median concentrations at least one order of magnitude lower than MP (63.5 μg/L) and PP (8.7 μg/L). Least-square geometric mean (LSGM) concentrations of MP were significantly higher (p ≤ 0.01) among non-Hispanic blacks than among non-Hispanic whites except at older ages (≥ 60 years). Adolescent and adult females had significantly higher (p < 0.01) LSGM concentrations of MP and PP than did adolescent and adult males. Females were more likely than males [adjusted odds ratios (ORs) and 95% confidence intervals (CIs): MP, 3.2 (2.99–5.27); PP, 4.19 (2.34–7.49)] and non-Hispanic blacks were more likely than non-Hispanic whites [MP, 4.99 (2.62–9.50); PP, 3.6 (1.86–7.05)] to have concentrations above the 95th percentile. Conclusions: The general U.S. population was exposed to several parabens during 2005–2006. Differences in the urinary concentration of MP and PP by sex and race/ethnicity likely reflect the use of personal care products containing these compounds.