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.

Development of dietary soluble fibres by enzymatic synthesis and assessment of their digestibility in in vitro, animal and randomised clinical trial models.

The aim was to develop novel fibres by enzymatic synthesis, to determine their total dietary fibre by AOAC method 2009.01 and to estimate their potential digestibility and assess their digestibility in vivo using glycaemic and insulinaemic responses as markers in mice and randomised clinical trial models. We found that fibre candidates to which α-(1,2) branching was added were resistant to digestion in the mouse model, depending on the amount of branching. These results show that in vivo models are needed to reliably assess the digestibility of α-glycosidic-linked oligomeric dietary fibre candidates, possibly due to absence of brush border α-glucosidase activity in the current in vitro assessment. α-(1,3)-linked and α-(1,6)-linked glucose oligomers were completely digested in humans and mice. In conclusion, it is possible to develop dietary soluble fibres by enzymatic synthesis. Adding α-(1,2) branching increases their resistance to digestion in vivo and can thus improve their suitability as potential fibre candidates. Clinical Trial Registry: ClinicalTrials.gov, NCT02701270.

Improved working memory performance following administration of a single dose of American ginseng (Panax quinquefolius L.) to healthy middle-age adults.

OBJECTIVE: A ginsenoside-rich extract of American ginseng (Panax quinquefolius L.), Cereboost(TM), was previously shown to improve working memory and mood in healthy young individuals. The present study represented a partial replication investigating whether these effects extended to healthy middle-aged individuals. METHODS: Fifty-two healthy volunteers (40-60 years old, mean age 51.63) received 200 mg of P. quinquefolius or a matching placebo according to a double-blind, placebo-controlled, balanced, crossover design. The Cognitive Drug Research battery and the Computerised Mental Performance Assessment System were used to evaluate cognitive performance at baseline then 1, 3 and 6 h following treatment. Blood glucose and mood were co-monitored. RESULTS: Compared with placebo, P. quinquefolius improved cognitive performance on 'Working Memory' factor at 3 h. Similar effects were observed in one of the two tasks making up this factor, spatial working memory. There were no significant effects on mood or blood glucose levels. CONCLUSIONS: These data confirm that P. quinquefolius can acutely benefit working memory and extend the age range of this effect to middle-aged individuals. These changes are unlikely to be underpinned by modulation of blood glucose in this population.

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.

A Healthy Vaginal Microbiota Remains Stable during Oral Probiotic Supplementation: A Randomised Controlled Trial.

The primary objective of this randomised, placebo-controlled, triple-blind study was to assess whether orally consumed Lactobacillus acidophilus La-14 (La-14) and Lacticaseibacillus rhamnosus HN001 (HN001) colonise a healthy human vagina. Furthermore, potential effects on vaginal microbiota and immune markers were explored. Fifty women devoid of vaginal complaints (Nugent score 0-3 and vaginal pH ≤ 4.5) were randomised into a 2-week intervention with either La-14 and HN001 as the verum product or a comparable placebo. Vaginal swab samples were collected at baseline, after one and two weeks of intervention, and after a one-week follow-up, for assessing colonisation of the supplemented lactobacilli, vaginal microbiota, and six specific immune markers. Colonisation of L. acidophilus and L. rhamnosus was not observed above the assay detection limit (5.29 and 5.11 log 10 genomes/swab for L. acidophilus and L. rhamnosus, respectively). Vaginal microbiotas remained stable and predominated by lactobacilli throughout the intervention, and vaginal pH remained optimal (at least 90% of participants in both groups had pH 4.0 or 4.5 throughout the study). Immune markers elafin and human ß-defensin 3 (HBD-3) were significantly decreased in the verum group (p = 0.022 and p = 0.028, respectively) but did not correlate with any microbiota changes. Adverse events raised no safety concerns, and no undesired changes in the vaginal microbiota or immune markers were detected.

Efficacy and safety of Lacticaseibacillus paracasei Lpc-37® in students facing examination stress: A randomized, triple-blind, placebo-controlled clinical trial (the ChillEx study).

Lacticaseibacillus paracasei Lpc-37 (Lpc-37) has previously shown to reduce perceived stress in healthy adults. The ChillEx study investigated whether Lpc-37 reduces stress in a model of chronic examination stress in healthy students. One hundred ninety university students (18-40 y) were randomized to take 1.56 × 1010 colony-forming units of Lpc-37 or placebo (1:1) each day for 10 weeks, in a triple-blind, parallel, multicenter clinical trial consisting of six visits: two screening visits, a baseline visit, and visits at 4, 8, and 10 weeks after baseline. The primary objective was to demonstrate that Lpc-37 reduces stress, as measured by the change in state anxiety from baseline to just before the first examination, after 8 weeks using the State Trait Anxiety Inventory (STAI-state). Secondary objectives aimed to demonstrate that Lpc-37 modulates psychological stress-induced symptoms and biomarkers related to mood and sleep. An exploratory analysis of fecal microbiota composition was also conducted. There was no difference between Lpc-37 and placebo groups in the change of STAI-state score (estimate 1.03; 95% confidence interval [CI]: -1.62, 3.67; p = 0.446). None of the secondary outcomes resulted in significant results when corrected for multiplicity, but exploratory results were notable. Results showed an improvement in sleep-disturbance scores (odds ratio 0.30; 95% CI: 0.11, 0.82; p = 0.020) and reduction in duration of sleep (odds ratio 3.52; 95% CI: 1.46, 8.54; p = 0.005) on the Pittsburgh Sleep Quality Index questionnaire after 8 weeks in the Lpc-37 group compared to placebo. A reduction in Bond Lader VAS-alertness was also demonstrated in the Lpc-37 group compared to placebo (estimate -3.97; 95% CI: -7.78, -0.15; p = 0.042) just prior to the examination. Analysis of fecal microbiota found no differences between study groups for alpha and beta diversity or microbiota abundance. Adverse events were similar between groups. Vital signs, safety-related laboratory measures, and gastrointestinal parameters were stable during the trial. In conclusion, probiotic Lpc-37 was safe but had no effect on stress, mood, or anxiety in healthy university students in this model of chronic academic stress. ClinicalTrials.gov: NCT04125810.

Bifidobacterium animalis subsp. lactis Bi-07 supports lactose digestion in vitro and in randomized, placebo- and lactase-controlled clinical trials.

BACKGROUND: Probiotics may alleviate lactose maldigestion. OBJECTIVES: The objective was to select a probiotic with high lactase activity and compare it with lactase and placebo in clinical trials. METHODS: Bacterial cultures were screened for lactase activity in a model of the upper gastrointestinal (GI) tract. Bifidobacterium animalis subsp. lactis Bi-07 (Bi-07) counts were adjusted in subsequent experiments to correspond to 4500 Food Chemicals Codex (FCC) units of lactase, the amount in the European Food Safety Authority (EFSA)-approved health claim. Two crossover clinical trials, Booster Alpha and Booster Omega, were performed in participants with lactose intolerance, where 2 × 1012 CFUs Bi-07, 4662 FCC lactase, or placebo was consumed simultaneously with a lactose challenge, with 1-wk washouts between challenges. The trial designs were identical except for the source of lactose. Breath hydrogen concentration (BHC) was measured to assess the effect of the investigational products on lactose digestion, for which incremental area under the curve (iAUC) was the primary outcome. Peak BHC, cumulative BHC, and GI symptoms were secondary outcomes. RESULTS: Bi-07 was superior to placebo in reducing BHC [iAUC, parts per million (ppm) ∙ h] in both trials (Booster Alpha: geometric least square mean ratio: 0.462; 95% CI: 0.249, 0.859; P = 0.016; Booster Omega: 0.227; 95% CI: 0.095, 0.543; P = 0.001). Lactase was superior to placebo in Booster Alpha (0.190; 95% CI: 0.102, 0.365; P < 0.001) but not Booster Omega (0.493; 95% CI: 0.210, 1.156; P = 0.102). Noninferiority of Bi-07 compared with lactase was observed in Booster Omega (0.460; 95% CI: 0.193, 1.096; P = 0.079; CI upper limit < 1.25 noninferiority margin). Odds of abdominal pain (compared with placebo: 0.32, P = 0.036) and flatulence (compared with placebo: 0.25, P = 0.007) were lower with lactase in Booster Alpha. Increased odds of nausea were seen with Bi-07 (compared with placebo: 4.0, P = 0.005) in Booster Omega. CONCLUSIONS: Bi-07 has high lactase activity, and in 2 clinical trials, it supported lactose digestion in individuals with lactose intolerance.These trials were registered at clinicaltrials.gov as NCT03659747 (Booster Alpha) and NCT03814668 (Booster Omega).

Carnosic acid-rich rosemary (Rosmarinus officinalis L.) leaf extract limits weight gain and improves cholesterol levels and glycaemia in mice on a high-fat diet.

Rosemary (Rosmarinus officinalis L.) extracts (RE) are natural antioxidants that are used in food, food supplements and cosmetic applications; exert anti-inflammatory and anti-hyperglycaemic effects; and promote weight loss, which can be exploited to develop new preventive strategies against metabolic disorders. Therefore, the aim of the present study was to evaluate the preventive effects of rosemary leaf extract that was standardised to 20 % carnosic acid (RE) on weight gain, glucose levels and lipid homeostasis in mice that had begun a high-fat diet (HFD) as juveniles. The animals were given a low-fat diet, a HFD or a HFD that was supplemented with 500 mg RE/kg body weight per d (mpk). Physiological and biochemical parameters were monitored for 16 weeks. Body and epididymal fat weight in animals on the HFD that was supplemented with RE increased 69 and 79 % less than those in the HFD group. Treatment with RE was associated with increased faecal fat excretion but not with decreased food intake. The extract also reduced fasting glycaemia and plasma cholesterol levels. In addition, we evaluated the inhibitory effects of RE in vitro on pancreatic lipase and PPAR-γ agonist activity; the in vitro findings correlated with our observations in the animal experiments. Thus, the present results suggest that RE that is rich in carnosic acid can be used as a preventive treatment against metabolic disorders, which merits further examination at physiological doses in randomised controlled trials.

Iridoids from Fraxinus excelsior with adipocyte differentiation-inhibitory and PPARalpha activation activity.

Two new secoiridoid glucosides, excelsides A (1) and B (2), were isolated from the seeds of Fraxinus excelsior. Their structures were elucidated as (2S,4S,3E)-methyl 3-ethylidene-4-(2-methoxy-2-oxoethyl)-2-[(6-O-beta-D-glucopyranosyl-beta-d-glucopyranosyl)oxy]-3,4-dihydro-2H-pyran-5-carboxylate and (2S,4S,3E)-methyl 3-ethylidene-4-{2-[2-(4-hydroxyphenyl)ethyl]oxy-2-oxoethyl}-2-[(6-O-beta-d-glucopyranosyl-beta-d-glucopyranosyl)oxy]-3,4-dihydro-2H-pyran-5-carboxylate, respectively, on the basis of NMR and MS data. Eight known compounds were identified as nuzhenide (3), GI3 (4), GI5 (5), ligstroside (6), oleoside 11-methyl ester (7), oleoside dimethyl ester (8), 1'''-O-beta-D-glucosylformoside (9), and salidroside (10). Compounds 1-9 inhibited adipocyte differentiation in 3T3-L1 cells. Dilutions of the aqueous extract of F. excelsior (1:10,000) as well as compounds 2, 3, 4, 5, and 8 activated the peroxisome proliferator-mediated receptor-alpha (PPARalpha) reporter cell system in the range of 10(-4) M, compared to 10(-7)-10(-8) M for the synthetic PPARalpha activator, WY14,643. Both biological activity profiles support the hypothesis that inhibition of adipocyte differentiation and PPARalpha-mediated mechanisms might be relevant pathways for the antidiabetic activity of F. excelsior extract.

Lacticaseibacillus paracasei Lpc-37® improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study).

Chronic stress is a risk-factor for the development of mood and stress-related disorders. Clinical evidence indicates that probiotics can influence the stress response and mood. The Sisu study investigated whether Lacticaseibacillus paracasei Lpc-37® (Lpc-37®) could modulate stress, mood and well-being. Prior to a two-week run-in period, 120 healthy adults (18-45 y) were stratified for sex and chronic stress and randomized to either 1.75 × 1010 colony forming units (CFU) of Lpc-37 or placebo (1:1) per day for 5 weeks. The primary objective was the effect of Lpc-37 on heart rate (HR) in response to the Trier Social Stress Test (TSST). Secondary objectives were assessed by biomarkers and self-report scales over the study. The primary hypothesis was not met in either the Intention-to-Treat (ITT) or Per Protocol (PP) population, but Lpc-37 reduced the increase in HR in participants with low chronic stress (LCS) and increased HR in participants with high chronic stress (HCS) during the TSST. Supporting significant efficacy in the PP population (n = 113), Lpc-37 reduced perceived stress following intervention. More significant effects were identified within the subgroups where Lpc-37 reduced exhaustion during the TSST and normalized cortisol levels at 8pm in participants with LCS, reduced perceived stress also in females, and increased perceived health and sleep-related recovery in participants with HCS. Adverse events (AEs) were similar between groups, there were no severe AEs, and vital signs remained unchanged. Overall, Lpc-37 reduced perceived stress compared to placebo. Other beneficial effects within biomarkers related to stress indicate that the effects of Lpc-37 may be differentially dependent on sex and chronic stress. (ClinicalTrials.gov: NCT03494725).

Grape extract improves antioxidant status and physical performance in elite male athletes.

Excessive physical exercise overproduces reactive oxygen species. Even if elite sportsmen increase their antioxidant status by regular physical training, during the competition period, this improvement is not sufficient to limit free radical production which could be detrimental to the body. The aim of this randomized, double-blind, placebo controlled, and crossover study on 20 elite sportsmen (handball = 10, basketball = 5, sprint = 4, and volleyball = 1) during the competition period was to determine if the consumption of a grape extract (GE; Vitis vinifera L.) was able to improve the parameters related to (i) anti-oxidative status and oxidative stress and (ii) physical performance. Specific biomarkers of antioxidant capacity, oxidative stress, skeletal cell muscle damage, and other general biomarkers were determined in plasma and urine before (D0) and after one month (D30) of placebo or GE supplementation (400mg·d(-1)). Effort tests were conducted using the Optojump(®) system, which allows determining the total physical performance (EnRJ45), explosive power (RJ110), and fatigue (RJL5). The plasma ORAC value was not modified in the placebo group; however, GE increased the ORAC value compared to the placebo at D30 (14 966+/-335 vs 14 242+/-339 dµmol Teq·L(-1); p < 0.05). The plasma FRAP value was significantly reduced in the placebo group, but not in the GE group. Therefore, GE limited the reduction of FRAP compared to the placebo at D30 (1 053.7+/-31.5 vs 993.7+/-26.7 µmol Teq·L(-1); p < 0.05). Urinary isoprostane values were increased in the placebo group, but were not modified in the GE group. Consequently, GE limited the production of isoprostanes compared to the placebo at D30 (1.24+/-0.12 vs 1.26+/-0.13 ng·mg(-1) creatinine; p < 0.05). GE administration, compared to the placebo at D30, reduced the plasmatic creatine phosphokinase concentration (CPK, 695.7+/-177.0 vs 480.0+/-81.1 IU·L(-1), p = 0.1) and increased hemoglobin levels (Hb, 14.5+/-0.2 vs 14.8+/-0.2 vs g·dL(-1), p < 0.05), suggesting that GE administration might protect cell damage during exercise. The high variability between sport disciplines did not permit to observe the differences in the effort test. Analyzing each individual group, handball players increased their physical performance by 24% (p < 0.05) and explosive power by 6.4% (p = 0.1) after GE supplementation compared to the placebo. Further analyses showed that CPK and Hb were the only biomarkers correlated with the increase in performance. In conclusion, GE ameliorates the oxidative stress/antioxidant status balance in elite athletes in the competition period, and enhances performance in one category of sportsmen (handball). Our results suggest that the enhancement in performance might be caused by the protective action of GE during physical exercise. These findings encourage conducting further studies to confirm the efficacy and mechanisms of action of GE on elite and occasional athletes. Key pointsGrape extract consumption improves the oxidative stress/antioxidant status balance in sportsmen.Grape extract consumption enhances physical performance in one category of sportsmen (Handball).The performance enhancement might be caused by the protective action of grape extract during physical exercise.

Efficacy of Polydextrose Supplementation on Colonic Transit Time, Bowel Movements, and Gastrointestinal Symptoms in Adults: A Double-Blind, Randomized, Placebo-Controlled Trial.

The addition of fiber is one of the most important dietary means to relieve constipation through lifestyle modification. Polydextrose (PDX) has been reported in several studies to increase fecal bulk, soften stools, and increase the number of defecations. However, there are few studies on the effect of PDX on colonic transit time (CTT). Therefore, the aim of this study was to demonstrate the effect of PDX on CTT and other aspects of gastrointestinal function during two weeks (Day 1 to Day 14), preceded by a 2-week run-in period (Day -14 to Day -1). A total of 192 adults who were diagnosed with functional constipation per Rome III criteria were recruited for the study. Participants were randomized equally into 4 groups (12 g, 8 g, or 4 g of PDX or placebo per day). The primary endpoint was CTT, assessed using radio-opaque markers and abdominal X-rays on Day 0, the baseline; and Day 15, the end of the intervention. Secondary outcomes that were measured using inventories were the patient assessment of constipation symptoms and quality of life, bowel function index, relief of constipation, bowel movement frequency (BMF), stool consistency, degree of straining, and proportion of bowel movements. Ancillary parameters and harms were also evaluated. The recruited population was not sufficiently constipated (e.g., baseline values for CTT and BMF of 42 h and 8.7 BMF/week, respectively). Despite this limitation, our results demonstrated an increased number of bowel movements when supplemented with PDX at a dosage of 12 g per day for 2 weeks. This dosage also consistently improved the secondary outcomes that were measured using inventories at Day 15, compared with the baseline. No serious or significant adverse events were reported during the study.

Influence of Lactitol and Psyllium on Bowel Function in Constipated Indian Volunteers: A Randomized, Controlled Trial.

Psyllium and lactitol have been reported to increase fecal volume, moisture content and bowel movement frequency (BMF). However, the benefits of their combined use on constipation has not been examined. The aim of this study was to evaluate the effects of a 4-week intervention with lactitol and/or psyllium on bowel function in constipated volunteers. Adults (N = 172) who were diagnosed with functional constipation per Rome III criteria were randomized to four treatment groups: 10 g lactitol, 3.5 g psyllium, a combination of 10 g lactitol and 3.5 g psyllium, or placebo. The primary endpoint was change in BMF from Day 0 to 28 as compared to placebo. Secondary endpoints were assessed by inventories, including stool consistency, patient assessment of constipation symptoms and quality of life, relief of constipation, 24-h food recall, physical activity, product satisfaction and adverse events (AE). BMF increased by 3.0 BMs with lactitol, by 2.9 with psyllium, and by 3.1 with the combination, but was not different from placebo (3.7 BMs). Other clinical endpoints were similar between treatments. No serious AEs were reported. In conclusion, this study showed a similar effect on relief of constipation in all treatment groups. The treatments that were administered to the volunteers were well tolerated.

Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation: A double-blind, randomized, placebo-controlled, and dose-ranging trial.

Bifidobacterium animalis subsp. lactis HN019 (HN019) ameliorates chronic idiopathic constipation. Our aim was to determine the efficacy and safety of 28-day supplementation with 1 × 109 or 1 × 1010 CFU of HN019/day for constipation. A total of 228 adults who were diagnosed with functional constipation according to the Rome III criteria were randomized in a double-blind and placebo-controlled trial. Colonic transit time (CTT), the primary outcome, and secondary outcomes that were measured using inventories-patient assessment of constipation symptoms (PAC-SYM) and quality of life (PAC-QoL), bowel function index (BFI), bowel movement frequency (BMF), stool consistency, degree of straining, bowel emptying, bloating, and pain severity-were assessed. Ancillary parameters and harms were also evaluated. There were no statistically significant differences in the primary or secondary outcomes between interventions. A post hoc analysis of 65 participants with fewer than 3 bowel movements per week (BMF ≤ 3/week) showed a physiologically relevant increase in weekly BMF in the high- (+2.0) and low-dose (+1.7) HN019 groups-by RMANOVA, the HN019 groups with BMF ≤ 3/week, pooled together, had a higher BMF versus placebo (P value = 0.01). Thus, improving low stool frequency could be a target of future interventions with HN019. High-dose HN019 also decreased the degree of straining at Day 28 versus placebo in those with BMF ≤ 3/week (P value = 0.02). Three unlikely related AEs-2 with low-dose HN019 and 1 with placebo-were followed until full recovery. In conclusion, although there were no differences in the primary analysis, HN019 is well tolerated and improves BMF in adults with low stool frequency.

A new process to develop a cocoa powder with higher flavonoid monomer content and enhanced bioavailability in healthy humans.

Cocoa is a food rich in polyphenols, mainly the flavonoid procyanidins and flavan-3-ols. The improvement of the cardiovascular function in humans upon cocoa consumption has been specifically linked to the presence of flavan-3-ol derived metabolites in plasma, especially epicatechin glucuronide. In this context, a flavonoid-enriched cocoa-derived product could potentially exert stronger health benefits. The aim of the present study was to obtain a cocoa powder with a higher flavonoid content (mainly enriched in monomer compounds) and assess its flavonoid bioavailability in humans. For this purpose, an unfermented, nonroasted, and blanch-treated cocoa powder (A) was obtained. The powder contained four times more procyanidins than a conventional (B) cocoa powder. Powder A contained eight times more epicatechin and procyanidin B2 than powder B. Cocoa milk drinks were prepared with powder A (MDA) and B (MDB). The bioavailability of flavonoids in both drinks was assessed in a crossover intervention with healthy volunteers. The content of epicatechin glucuronide, the main metabolite detected in plasma, was five-fold higher upon consumption of MDA as compared with MDB. The urinary excretion of metabolites, mainly methyl epicatechin sulfate, was higher upon MDA consumption as compared with MDB, ranging from two- to 12-fold higher depending on the metabolite. These results, together with previous reports regarding the cardiovascular benefits linked to the presence of procyanidin metabolites in plasma, suggest that further clinical trials to validate the health benefits of a flavonoid-enriched cocoa powder are warranted.

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 probiotic-containing products on stool frequency and intestinal transit in constipated adults: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Probiotics are commonly recommended for the alleviation of constipation symptoms. The aim of this research was to determine the effects of probiotic-containing products on stool frequency and intestinal transit time (ITT) in constipated adults and to determine the factors that influence the efficacy of these products. METHODS: We conducted a systematic review of randomized controlled trials that measured weekly stool frequency or ITT in constipated adults receiving probiotic-containing supplements. A random effects meta-analysis was performed; stool frequency was summarized by the mean difference statistic and ITT was summarized by the standardized mean difference (SMD) statistic. Meta-regression and diagnostic model performance testing were used to identify publication bias and sources of heterogeneity. RESULTS: A total of 21 studies (23 comparisons) comprising 2656 subjects were included. All studies utilized probiotics containing Lactobacillus or Bifidobacterium species. Probiotic-containing products resulted in a mean increase in weekly stool frequency of 0.83 (95% confidence interval [CI] 0.53-1.14, P<0.001). There was high heterogeneity among the studies (I2=85%, P<0.001) and evidence of significant publication bias (Egger's P-value <0.01). After adjustment for publication bias, the mean difference in weekly stool frequency was reduced from 0.83 to 0.30. The effects on stool frequency were greater in studies where functional constipation was diagnosed using Rome III (P<0.01), or Rome II or III criteria (P<0.05), compared to non-Rome diagnosis techniques. Probiotic-containing products were also efficacious in reducing ITT (SMD=0.65, 95%CI 0.33-0.97, P<0.001). There was high heterogeneity among studies (I2=66%, P<0.01), but no evidence of publication bias (Egger's P-value=0.52). A larger total sample size was associated with greater efficacy as regards ITT (P=0.03). The probiotic species, the number of probiotic strains and the daily probiotic dosage had no influence on the outcomes. CONCLUSION: Supplementation with products containing Lactobacillus or Bifidobacterium species increases stool frequency and reduces ITT in constipated adults. However, since significant heterogeneity in outcomes was detected among the studies analyzed, the results should be interpreted with caution.

Normative Values for Colonic Transit Time and Patient Assessment of Constipation in Adults With Functional Constipation: Systematic Review With Meta-Analysis.

Availability of normative patient outcome data may assist in designing experiments and estimating sample sizes. The purpose of this review was to determine normative ranges for colonic transit time (CTT), Patient Assessment of Constipation-Symptoms (PAC-SYM), and Patient Assessment of Constipation-Quality of Life (PAC-QOL) in adults diagnosed with functional constipation per Rome III guidelines. Pooled estimates were derived from random-effects meta-analysis. Meta-regression was used to explore sources of heterogeneity among studies. A total of 24 studies (3786 patients) were included in the review. In 10 studies with 1119 patients, pooled CTT was 58 hours (95% confidence interval [CI]: 50-65 hours). Publication bias was not evident (Egger P = .51); heterogeneity was high (I2 = 92%, P < .001). In meta-regression, geographical location explained 57% of the between-study variance, with CTT significantly longer in studies conducted in Europe (71 hours) compared with Asia (49 hours) or the Americas (44 hours). In 9 studies with 2061 patients, pooled PAC-SYM was 1.70 (95% CI: 1.58-1.83). Publication bias was not evident (Egger P = .44). Heterogeneity was high (I2 = 90%, P < .001); however, no study or patient factor influenced PAC-SYM in meta-regression. In 12 studies with 1805 patients, pooled PAC-QOL was 1.97 (95% CI: 1.70-2.24). Publication bias was not evident (Egger P = .28); heterogeneity was high (I2 = 98%, P < .001). In meta-regression, age explained 52% of the between-study variance, with older age associated with lower PAC-QOL scores. Overall, in adults diagnosed with functional constipation per Rome III criteria, significant heterogeneity in CTT, PAC-SYM, and PAC-QOL exists among studies. Variability among studies may be explained by geography and patient factors.

Normative values for stool frequency and form using Rome III diagnostic criteria for functional constipation in adults: systematic review with meta-analysis.

When designing clinical trials focused on functional constipation therapies, understanding the normative values of populations selected using the Rome III criteria is important for estimating baseline symptom severity, and for power analysis and sample size calculations. The objective of this review was to determine normative ranges for stool frequency and form in adults with functional constipation (Rome III criteria). Eligible studies reported stool frequency or form; random effects meta-analysis was performed with subgroup analyses to explore sources of heterogeneity. A total of 25 studies (43 groups, 2292 subjects) were included. Pooled estimates were 2.7 (95% CI 2.4-3.0) for weekly stools and 2.4 (95% CI 2.1-2.6) for stool form (Bristol scale). Heterogeneity was high for both outcomes (both I2=96%, P<0.001). Subgroup analysis revealed that weekly bowel movement frequency was higher in larger than in smaller studies (3.1 vs. 2.3, P<0.001) and in studies conducted in Europe compared with those in the Americas (3.1 vs. 2.2, P=0.02). For stool form, the use of a daily diary versus subject recall was the sole explanatory variable (2.5 vs. 2.1, P<0.05). We conclude that adults with functional constipation have significant variation in stool frequency and form, explained in part by geography and study design.