Correcting for non-compliance when determining colonic transit time with radio-opaque markers.

The use of radio-opaque markers and abdominal X-ray is the standard method for determining colonic transit time (CTT). However, when there are deviations in the intake of these markers by participants in clinical trials it is desirable to improve observations by introducing corrections, where possible. To date, there is no standard procedure to adjust for such deviations. This report proposes a series of alternatives based on possible scenarios for deviations from the intended intake of radio-opaque markers. The proposed method to correct for missed or delayed consumption of radio-opaque markers can help to increase the accuracy of the CTT measurements in clinical trials.

Effects of polydextrose with breakfast or with a midmorning preload on food intake and other appetite-related parameters in healthy normal-weight and overweight females: An acute, randomized, double-blind, placebo-controlled, and crossover study.

Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females. Per earlier studies, the primary outcome was defined as the difference in subsequent EI when PDX was consumed at midmorning versus placebo. Thirty-two volunteers were enrolled in this acute, double-blind, placebo-controlled, randomized, and crossover trial to examine the effects of 12.5 g of PDX, administered as part of a breakfast or midmorning preload, on subsequent EI, subjective feelings of appetite, well-being, and mood. Gastric emptying rates and the blood concentrations of glucose, insulin, cholecystokinin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine-tyrosine were measured in the group that received PDX as part of their breakfast. There were no differences in EI between volunteers who were fed PDX and placebo. PDX intake with breakfast tended to elevate blood glucose (P = 0.06) during the postabsorptive phase, significantly lowered insulin by 15.7% (P = 0.04), and increased GLP-1 by 39.9% (P = 0.02); no other effects on blood parameters or gastric emptying rates were observed. PDX intake at midmorning reduced hunger by 31.4% during the satiation period (P = 0.02); all other subjective feelings of appetite were unaffected. Volunteers had a uniform mood profile during the study. PDX was well tolerated, causing one mild adverse event throughout the trial.

Independent and Combined Effects of Lactitol, Polydextrose, and Bacteroides thetaiotaomicron on Postprandial Metabolism and Body Weight in Rats Fed a High-Fat Diet.

Obesity is related to the consumption of energy-dense foods in addition to changes in the microbiome where a higher abundance of gut Bacteroidetes can be found in lean subjects or after weight loss. Lactitol, a sweet-tasting sugar alcohol, is a common sugar-replacement in foods. Polydextrose (PDX), a highly branched glucose polymer, is known to reduce energy intake. Here, we test if the combined effects of lactitol or PDX in combination with Bacteroides species will have a beneficial metabolic response in rats fed a high-fat (HF) diet. A total of 175 male Wistar rats were fed either a LF or HF diet. Bacteroides thetaiotaomicron (10(10) bacteria/animal/day) was orally administered with or without lactitol (1.6-2 g/animal/day) or PDX (2 g/animal/day) for 8 days. Postprandial blood samples, cecal digesta, and feces were collected on the last day. Measurements included: body weight, feed consumption, cecal short-chain fatty acids, fecal dry matter and heat value, blood glucose, insulin, triglyceride, and satiety hormone concentrations. Lactitol and PDX decreased the mean body weight when administered with B. thetaiotaomicron or when lactitol was administered alone. Levels of postprandial plasma triglycerides declined with lactitol and PDX when administered with B. thetaiotaomicron. For intestinal hormone release, lactitol - alone or with B. thetaiotaomicron - increased the release of gastrointestinal peptide tyrosine tyrosine (PYY) as well as the area under the curve (AUC) measured for PYY (0-8 h). In addition, levels of insulin AUC (0-8 h) decreased in the lactitol and PDX-supplemented groups. Lactitol and PDX may both provide additional means to regulate postprandial metabolism and weight management, whereas the addition of B. thetaiotaomicron in the tested doses had only minor effects on the measured parameters.

Effect of Polydextrose on Subjective Feelings of Appetite during the Satiation and Satiety Periods: A Systematic Review and Meta-Analysis.

INTRODUCTION: Subjective feelings of appetite are measured using visual analogue scales (VAS) in controlled trials. However, the methods used to analyze VAS during the Satiation (pre- to post-meal) and Satiety (post-meal to subsequent meal) periods vary broadly, making it difficult to compare results amongst independent studies testing the same product. This review proposes a methodology to analyze VAS during both the Satiation and Satiety periods, allowing us to compare results in a meta-analysis. METHODS: A methodology to express VAS results as incremental areas under the curve (iAUC) for both the Satiation and Satiety periods is proposed using polydextrose as a case study. Further, a systematic review and meta-analysis on subjective feelings of appetite was conducted following the PRISMA methodology. Meta-analyses were expressed as Standardized Mean Difference (SMD). RESULTS: Seven studies were included in the meta-analysis. There were important differences in the methods used to analyze appetite ratings amongst these studies. The separate subjective feelings of appetite reported were Hunger, Satisfaction, Fullness, Prospective Food Consumption, and the Desire to Eat. The method proposed here allowed the results of the different studies to be homogenized. The meta-analysis showed that Desire to Eat during the Satiation period favors polydextrose for the reduction of this subjective feeling of appetite (SMD = 0.24, I² < 0.01, p = 0.018); this effect was also significant in the sub-analysis by sex for the male population (SMD = 0.35, I² < 0.01, p = 0.015). There were no other significant results. CONCLUSION: It is possible to compare VAS results from separate studies. The assessment of iAUC for both the Satiation and Satiety periods generates results of homogeneous magnitudes. This case study demonstrates, for the first time, that polydextrose reduces the Desire to Eat during the Satiation period. This may explain, at least in part, the observed effects of polydextrose on the reduction of levels of energy intake at subsequent meals.

Postprandial effects of polydextrose on satiety hormone responses and subjective feelings of appetite in obese participants.

BACKGROUND: Dietary fibers are associated with enhanced satiety. However, the mechanism of different dietary fibers contributing to satiety-related gastrointestinal (GI) peptide release, especially in an obese population, is still poorly understood. Polydextrose (PDX), a water-soluble glucose polymer, has demonstrated its ability to reduce energy intake at a subsequent meal, but its mechanism of action requires further research. Also, there is limited evidence on its capacity to regulate subjective feelings of appetite. This study examines the effects of PDX on postprandial secretion of satiety-related GI peptides, short chain fatty acids (SCFAs), lactic acid, and subjective appetite ratings in obese participants. METHODS: 18 non-diabetic, obese participants (42.0 y, 33.6 kg/m2) consumed a high-fat meal (4293 kJ, 36% from fat) with or without PDX (15 g) in an acute, multicenter, randomized, double-blind, placebo-controlled and crossover trial. Postprandial plasma concentrations of satiety-related peptides, namely ghrelin, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), as well as SCFAs and lactic acid were assessed. GI peptide, SCFA and lactate concentrations were then modeled using a linear mixed-effects model.The subjective feelings of hunger, satisfaction, and desire to eat were evaluated using visual analogue scales (VAS), which were analyzed as incremental areas under the curve (iAUC) during the satiation and satiety periods. RESULTS: We found that PDX supplementation increased plasma GLP-1 levels more than the placebo treatment (P = 0.02). In the whole group, GLP-1 concentrations found in participants older than 40 years old were significantly lower (P = 0.01) as compared to those aged 40 years or less. There were no statistically significant differences in postprandial ghrelin, CCK, or PYY responses. The lactic acid concentrations were significantly (P = 0.01) decreased in the PDX group, while no significant changes in SCFAs were found. PDX reduced iAUC for hunger by 40% (P = 0.03) and marginally increased satisfaction by 22.5% (P = 0.08) during the post-meal satiety period. CONCLUSION: Polydextrose increased the postprandial secretion of the satiety hormone GLP-1 and reduced hunger after a high-fat meal. PDX also reduced the elevated postprandial lactic acid levels in plasma. Therefore, PDX may offer an additional means to regulate inter-meal satiety and improve postprandial metabolism in obese participants.

Effects of polydextrose on different levels of energy intake. A systematic review and meta-analysis.

INTRODUCTION: Dietary fibers help to control energy intake and reduce the risk of developing obesity. Recent studies show that the consumption of polydextrose reduces energy intake at a subsequent meal. In this systematic review and meta-analysis we examine the subsequent effects of polydextrose on different levels of energy intake (EI). METHOD: The review followed the PRISMA methodology. Meta-analyses were expressed as Standardized Mean Difference (SMD). A linear regression approach was used to model the relationship between the polydextrose dose and the different levels of EI expressed as a relative change (%). RESULTS: All the studies included in this review administered polydextrose as part of a mid-morning snack. Six studies were included in the analysis of EI at an ad libitum lunch; and three were included in the analysis of EI during the rest of the day, as well as total daily EI. The meta-analysis showed that the consumption of polydextrose is associated with a reduction in EI at lunch time (SMD = 0.35; P <0.01; I(2) = 0). The dose of polydextrose consumed correlated significantly with this reduction in EI, EILunch (%) = -0.67 Polydextrose (g/day) (R(2) = 0.80; P <0.01). The meta-analysis of EI during the rest of the day and daily EI did not show any difference. Nevertheless, the regression equation indicates that there is a dose-dependent effect on the reduction of daily EI, EIDaily (%) = -0.35 × Polydextrose (g/day) (R(2) = 0.68; P <0.05). Sex-specific results are consistent with results for the whole group. CONCLUSION: The studies included in this meta-analysis support the notion that the consumption of polydextrose reduces voluntary energy intake at a subsequent meal. Furthermore, this reduction in energy intake occurs in a dose-dependent manner.

Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach.

SCOPE: Betaine (BET) reduces diet-induced liver lipid accumulation, and may relieve obesity-related metabolic disturbances. The aim of our study was to analyze metabolite alterations after supplementation of BET, polydextrose (PDX, a soluble dietary fiber), or their combination (BET PDX) via drinking water to C57BL/6J mice fed a high-fat (HF) diet. METHODS AND RESULTS: BET supplementation increased BET levels in plasma, muscle, and liver (p < 0.05), and the nontargeted LC-MS metabolite profiling revealed an increase in several metabolites in the carnitine biosynthesis pathway after BET supplementation both in liver and muscle. These included carnitine and acetylcarnitine (1.4-fold, p < 0.05), propionylcarnitine and γ-butyrobetaine (1.5-fold, p < 0.05), and several other short-chain acylcarnitines (p < 0.05) in muscle. These changes were slightly higher in the BET PDX group. Furthermore, BET reduced the HF diet induced accumulation of triglycerides in liver (p < 0.05). The supplementations did not attenuate the HF diet induced increase in body weight gain or the increase in adipose tissue mass. Instead, the combination of BET and PDX tended to increase adiposity. CONCLUSION: Our results suggest that increased availability of BET in different tissues, especially in muscle, after BET supplementation has an impact on carnitine metabolism, and this could further explain the link between BET and lipid metabolism.

Bifidobacterium animalis ssp. lactis 420 Protects against Indomethacin-Induced Gastric Permeability in Rats.

Gastrointestinal (GI) adverse effects such as erosion and increased permeability are common during the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Our objective was to assess whether Bifidobacterium animalis ssp. lactis 420 protects against NSAID-induced GI side effects in a rat model. A total of 120 male Wistar rats were allocated into groups designated as control, NSAID, and probiotic. The NSAID and probiotic groups were challenged with indomethacin (10 mg/kg(-1); single dose). The probiotic group was also supplemented daily with 10(10) CFU of B. lactis 420 for seven days prior to the indomethacin administration. The control group rats received no indomethacin or probiotic. The permeability of the rat intestine was analysed using carbohydrate probes and the visual damage of the rat stomach mucosa was graded according to severity. B. lactis 420 significantly reduced the indomethacin-induced increase in stomach permeability. However, the protective effect on the visual mucosal damage was not significant. The incidence of severe NSAID-induced lesions was, nevertheless, reduced from 50% to 33% with the probiotic treatment. To conclude, the B. lactis 420 supplementation protected the rats from an NSAID-induced increase in stomach permeability and may reduce the formation of more serious GI mucosal damage and/or enhance the recovery rate of the stomach mucosa.

Impact of polydextrose on the faecal microbiota: a double-blind, crossover, placebo-controlled feeding study in healthy human subjects.

In this placebo-controlled, double-blind, crossover human feeding study, the effects of polydextrose (PDX; 8 g/d) on the colonic microbial composition, immune parameters, bowel habits and quality of life were investigated. PDX is a complex glucose oligomer used as a sugar replacer. The main goal of the present study was to identify the microbial groups affected by PDX fermentation in the colon. PDX was shown to significantly increase the known butyrate producer Ruminococcus intestinalis and bacteria of the Clostridium clusters I, II and IV. Of the other microbial groups investigated, decreases in the faecal Lactobacillus-Enterococcus group were demonstrated. Denaturing gel gradient electrophoresis analysis showed that bacterial profiles between PDX and placebo treatments were significantly different. PDX was shown to be slowly degraded in the colon, and the fermentation significantly reduced the genotoxicity of the faecal water. PDX also affected bowel habits of the subjects, as less abdominal discomfort was recorded and there was a trend for less hard and more formed stools during PDX consumption. Furthermore, reduced snacking was observed upon PDX consumption. This study demonstrated the impact of PDX on the colonic microbiota and showed some potential for reducing the risk factors that may be associated with colon cancer initiation.

Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor.

BACKGROUND: Nuclear localization of proteolytically formed intracellular fragment of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and nuclear localization of ErbB4 receptor has been described in human breast cancer. Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic cascade leading to ErbB4 intracellular domain formation. Interactions between matrix metalloproteases and heparan sulfate have been described, but the effect of cell surface heparan sulfate on TACE activity has not been previously described. RESULTS: As indicated by immunodetection of increased ErbB4 intracellular domain formation and direct enzyme activity analysis, TACE activity was substantially amplified by enzymatic removal of cell surface heparan sulfate but not chondroitin sulfate. CONCLUSION: In this communication, we suggest a novel role for cell surface heparan sulfate. Removal of cell surface heparan sulfate led to increased formation of ErbB4 intracellular domain. As ErbB4 intracellular domain has previously been shown to promote cell survival this finding may indicate a novel mechanism how HS degradation active in tumor tissue may favor cell survival.