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).

The Probiotic Strain H. alvei HA4597® Improves Weight Loss in Overweight Subjects under Moderate Hypocaloric Diet: A Proof-of-Concept, Multicenter Randomized, Double-Blind Placebo-Controlled Study.

Background: Increasing evidence supports the role of the gut microbiota in the control of body weight and feeding behavior. Moreover, recent studies have reported that the probiotic strain Hafnia alvei HA4597® (HA), which produces the satietogenic peptide ClpB mimicking the effect of alpha-MSH, reduced weight gain and adiposity in rodent models of obesity. Methods: To investigate the clinical efficacy of HA, 236 overweight subjects were included, after written informed consent, in a 12-week prospective, double-blind, randomized study. All subjects received standardized counselling for a -20% hypocaloric diet and were asked to maintain their usual physical activity. Subjects of the HA group received two capsules per day providing 100 billion bacteria per day and subjects in the Placebo (P) group received two placebo capsules. The primary endpoint was the percentage of subjects achieving a weight loss of at least 3% after 12 weeks. Intention-to-treat statistical analysis was performed using exact-Fischer, Mann-Whitney and paired-Wilcoxon tests as appropriate. Results: In the HA group, significantly more subjects (+33%) met the primary endpoint than in the P group (54.9 vs. 41.4%, p = 0.048). In the HA group, an increased feeling of fullness (p = 0.009) and a greater loss of hip circumference (p < 0.001) at 12 weeks were also observed. Fasting glycemia at 12 weeks was significantly lower (p < 0.05) in the HA compared to P group. Clinical and biological tolerance was good in both groups. Conclusions: A 12-week treatment with the probiotic strain H. alvei HA4597® significantly improves weight loss, feeling of fullness and reduction of hip circumference in overweight subjects following moderate hypocaloric diet. These data support the use of H. alvei HA4597® in the global management of excess weight.

Development of an Affordable, Sustainable and Efficacious Plant-Based Immunomodulatory Food Ingredient Based on Bell Pepper or Carrot RG-I Pectic Polysaccharides.

The prevalence of acute respiratory infections and their impact on quality of life underlies the need for efficacious solutions that are safe, sustainable and economically viable. Polysaccharides in several (traditional) plant extracts have been shown to be immunostimulatory, and some studies suggest beneficial effects against respiratory infections. The aim of this study was to (i) identify the active polysaccharide constituents from affordable and renewable crops (bell pepper and carrot) using activity-guided fractionation, (ii) evaluate in vitro effects on innate immune responses (phagocytosis and cytokine secretion), microbiota modulation and production of short chain fatty acids, followed by (iii) the evaluation of effects of a bell pepper extract enriched for the active component in a human proof of concept study. We identified rhamnogalacturonan-I (RG-I) as the nutricophore responsible for the immunostimulatory activity with substantial structural and functional equivalence between bell pepper (bp) and carrot (c). The in vitro studies showed that bpRG-I and cRG-I comprise similar immune- and microbiota modulatory potential and the human study demonstrated that bpRG-I was well tolerated and enhanced innate immune responsiveness in vivo. This is an important step towards testing the efficacy of RG-I from bpRG-I or cRG-I in an infection trial in humans.

Investigation of the natural supplement IQP-AS-119 for the prevention of upper respiratory tract infections in marathon race participants: A randomized, double-blind, placebo-controlled pilot study.

Intense and prolonged exercise leads to immune suppression, causing upper respiratory tract infections (URTI). A proprietary standardized dietary supplement, IQP-AS-119 has been previously developed to aid immune responses under such conditions. The current randomized, double-blind, placebo-controlled pilot study aimed to investigate the effects of IQP-AS-119 on marathon runners. A total of 80 participants were randomized equally into groups receiving either placebo (P group) or IQP-AS-119 (V group) treatment, starting 3 weeks before and for 14 days after the marathon. Benefit assessment was performed using different questionnaires. Post-marathon, the V and P groups reported 1±2.38 and 2.11±3.25 days with upper respiratory tract symptoms (URTS), respectively (P=0.038). During the 14 days post-marathon, 20.0% of the participants in the V group compared with 44.4% in the P group reported URTS (P=0.042). The V group reported significantly milder URTS compared with the P group on Days 9, 12, 13 and 14 post-marathon (P<0.05). The total Perceived Stress Questionnaire-20 score on days 2-14 were significantly lower for the V group compared with the P group (P=0.035). In the Short Form 12 Health Survey, the V group exhibited significant improvement in mental composite score on days -5 to 14 compared with the P group (P=0.038). In the overall treatment effect assessment, there were no statistically significant differences between the groups. The IQP-AS-119 was rated 'very good' or 'good' by investigators and participants, respectively, for 71 and 65% of the participants. The tolerability of IQP-AS-119 was rated as 'very good' or 'good' by both investigators and 95% of participants. No clinically relevant differences were observed between groups regarding adverse events or other safety parameters. Therefore, IQP-AS-119 was demonstrated to reduce the incidence and severity of URTI in marathon runners. Given its good tolerability profile, IQP-AS-119 may be a good nutritional supplement for the reduction of URTS in susceptible individuals.

Effects of aged garlic extract on arterial elasticity in a placebo-controlled clinical trial using EndoPAT™ technology.

Cardiovascular diseases are the main cause of death in the industrialized world, with the main risk factors being elevated blood pressure and blood lipid levels, leading to arterial stiffness and arteriosclerosis. In this study, we examined the effect of aged garlic extract (AGE) on arterial elasticity, using the EndoPAT™ technology in subjects with slightly elevated blood pressure. This randomized double-blind, placebo-controlled clinical trial examined 57 subjects over a period of 12 weeks, with EndoPAT™ measurements taken at 0 and 12 weeks; in addition, changes in blood pressure were analyzed. The positive effect of AGE on blood pressure values previously reported was confirmed. The results revealed a significant decrease in blood pressure in the AGE group, and in particular diastolic blood pressure. Using the EndoPAT™ technology, the augmentation index (AI) was analyzed, which measures arterial stiffness calculated via pulse waveform analysis of the PAT signal; lower AI values reflect better arterial elasticity. The AGE group exhibited a significant improvement in arterial elasticity, measured as AI75, by 21.6%. The result of this well-controlled clinical trial confirmed the positive effect of AGE on blood pressure. To the best of our knowledge, for the first time, the effect of AGE on arterial elasticity could be proven using the EndoPAT™ methodology. These results not only demonstrate the positive effects of AGE on the relevant risk factors of cardiovascular diseases, but also the direct effect on arterial elasticity. These data clearly indicate that AGE may exert several positive direct effects on the development and progression of cardiovascular diseases.

A Dose-Escalation Study Demonstrates the Safety and Tolerability of Cellobiose in Healthy Subjects.

The disaccharide and innovative ingredient cellobiose, consisting of two ß-glucose molecules linked by a ß(1→4) bond is the main component of cellulose. Cellobiose can be used within a wide variety of foodstuffs and functional foods as a low-caloric bulking agent or as a substitute for lactose. For purposes of industrial large-scale production, cellobiose is produced by an enzymatic reaction in which sucrose and glucose are converted to cellobiose and fructose. The goal of this single-arm, dose-escalation study was to evaluate the safety and tolerability of cellobiose and to determine the maximum tolerated dose of cellobiose in healthy subjects. Following a baseline period, consecutive cohorts of six subjects each consumed either single doses of 10, 15, 20 and 25 g, while 12 subjects each received multiple doses of 15 g or 20 g cellobiose (twice daily, 14 days). The main recorded parameters were stool consistency, gastrointestinal well-being (Gastrointestinal Symptom Rating Scale) and adverse events. In each highest single/multiple dosage group, some sensitive subjects experienced flatulence, borborygmus and/or transient diarrhoea. A 100% global tolerability rating makes 20 g cellobiose a tolerable dose for single use. For repeated consumption, we propose up to 15 g cellobiose twice daily (92.6% global tolerability rating). Cellobiose is a promising new ingredient with excellent tolerability.

Erratum to "Double-Blind, Randomized, Three-Armed, Placebo-Controlled, Clinical Investigation to Evaluate the Benefit and Tolerability of Two Dosages of IQP-AE-103 in Reducing Body Weight in Overweight and Moderately Obese Subjects".

[This corrects the article DOI: 10.1155/2019/3412952.].

Sleep Promoting Effects of IQP-AO-101: A Double-Blind, Randomized, Placebo-Controlled Exploratory Trial.

OBJECTIVE: The purpose of this study was to explore the clinical benefit and tolerability of IQP-AO-101 in healthy subjects with sleep complaints. METHODS: This double-blind, randomized, placebo-controlled trial involved fifty subjects with sleep complaints. Subjects with a Pittsburgh Sleep Quality Index (PSQI) score between 6 and 15 were randomized to receive either IQP-AO-101 or placebo for 6 weeks, following a run-in period of one week. Sleep parameters were assessed at baseline and after 1, 4, and 6 weeks using the modified Athens Insomnia Scale (mAIS). Subjects were also instructed to wear an activity tracker and keep a sleep diary during the study. Other questionnaires administered were the Frankfurt Attention Inventory (FAIR-2) and the Profile of Mood States (POMS-65). Blood samples for safety laboratory parameters were taken before and at the end of the study. RESULTS: After 6 weeks, subjects who consumed IQP-AO-101 reported significant improvements in mAIS scores compared with placebo, including mAIS total score (11.76 ± 6.85 vs 4.00 ± 4.80; p < 0.001); night parameters composite score (5.20 ± 3.80 vs 2.04 ± 3.16; p = 0.001); and day parameters composite score (6.56 ± 4.10 vs 1.96 ± 2.65; p < 0.001). All individual parameters (Items 1 to 8) were also significantly improved from baseline after 6 weeks of IQP-AO-101 intake. Analysis of variance with baseline values as covariates showed statistically significant improvements across all individual parameters for IQP-AO-101 when compared to placebo. The measurements using the activity tracker, sleep diary, FAIR-2, and POMS did not reveal any significant differences between groups. No adverse effects related to the intake of IQP-AO-101 were reported. Tolerability was rated as very good by all the subjects and by the investigator for all cases. CONCLUSIONS: In this study, IQP-AO-101 was well tolerated and efficacious for promoting sleep and enhancing daytime performance in subjects with moderate sleep disturbances. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, no. NCT03114696.

Double-Blind, Randomized, Three-Armed, Placebo-Controlled, Clinical Investigation to Evaluate the Benefit and Tolerability of Two Dosages of IQP-AE-103 in Reducing Body Weight in Overweight and Moderately Obese Subjects.

Objective: This study was performed to determine the efficacy and tolerability/safety of IQP-AE-103 on body weight reduction in overweight to moderately obese adults. Methods: A double-blind, randomized, placebo-controlled trial involved one hundred and eight subjects (BMI between 25 and 35 kg/m2) that were randomly assigned to either the low-dose or the high-dose IQP-AE-103 group, or the placebo group. Following a 2-week run-in period, subjects received two capsules of investigational product after three daily main meals for 12 weeks. Subjects were instructed to maintain a nutritionally balanced hypocaloric diet according to the individual's energy requirement. Body weight, body fat, and waist and hip circumference were measured at baseline, and after 2, 4, 8, and 12 weeks. Subjects also rated their feelings of hunger and fullness using visual analogue scales, and food craving on a 5-point scale at the same time intervals. Blood samplings for safety laboratory parameters were taken before and at the end of the study. Results: After 12 weeks of intake, the high-dose IQP-AE-103 group had a significantly greater weight loss compared with the placebo (5.03 ± 2.50 kg vs. 0.98 ± 2.06 kg, respectively; p < 0.001) and the low-dose group (3.01 ± 2.19 kg; p=0.001). The high-dose group experienced a decrease in body fat of 3.15 ± 2.41 kg compared with a decrease of 0.23 ± 2.74 kg for the placebo group (p < 0.001). High-dose IQP-AE-103 also decreased the feeling of hunger in 66% subjects. A beneficial effect of IQP-AE-103 on the lipid metabolism was also demonstrated in the subgroup of subjects with baseline total cholesterol levels above 6.2 mmol/L. No side effects related to the intake of IQP-AE-103 were reported. Conclusions: These findings indicate that IQP-AE-103 could be an effective and safe weight loss intervention. This trial is registered with NCT03058367.

Efficacy and safety of a natural mineral water rich in magnesium and sulphate for bowel function: a double-blind, randomized, placebo-controlled study.

PURPOSE: The present placebo-controlled, double-blind, randomized trial aimed to investigate whether a natural mineral water rich in magnesium sulphate and sodium sulphate (Donat Mg) may help to improve bowel function. METHODS: A total of 106 otherwise healthy subjects with functional constipation were randomly assigned to consume 300 or 500 mL of a natural mineral water as compared to placebo water, over a course of 6 weeks. The 300-mL arms were terminated due to the results of a planned interim analysis. Subjects documented the complete spontaneous bowel movements, spontaneous and overall bowel movements/week, stool consistency, gastrointestinal symptoms and general well-being in a diary. Change in the number of complete spontaneous bowel movements was defined as the primary outcome. RESULTS: For the 75 subjects in the 500-mL arms, the change in the number of complete spontaneous bowel movements per week tended to be higher in the active group when compared to placebo after 6 weeks (T2 = 1.8; p value = 0.036; one-sided). The mean number of spontaneous bowel movements significantly increased over the course of the study, with significant differences between study arms considering the whole study time (F test = 4.743; p time × group = 0.010, 2-sided). Stool consistency of spontaneous bowel movements (p < 0.001) and the subjectively perceived symptoms concerning constipation (p = 0.005) improved significantly with the natural mineral water as compared to placebo. CONCLUSIONS: The daily consumption of a natural mineral water rich in magnesium sulphate and sodium sulphate improved bowel movement frequency and stool consistency in subjects with functional constipation. Moreover, the subjects' health-related quality of life improved. CLINICAL TRIAL REGISTRATION: EudraCT No 2012-005130-11.

Safety and efficacy of Nasya/Prevalin in reducing symptoms of allergic rhinitis.

BACKGROUND: Nasya/Prevalin is a natural, drug-free nasal spray for treatment and prevention of allergic rhinitis. Because of its thixotropic property, it forms a barrier on the nasal mucosa, preventing allergen contact. This study assesses the clinical efficacy and safety of Nasya/Prevalin in a nasal provocation test with house dust mite allergens. METHODOLOGY/PRINCIPAL: In this randomised, double-blind, placebo-controlled trial, 20 subjects suffering from allergic rhinitis because of house dust mite allergens received a single dose of Nasya/Prevalin or saline spray before allergen challenge. Total nasal symptom score and total ocular symptom score were assessed 15, 30, 60, 75, 90, 120 and 240 min after challenge. Further, the appearance of the mucosa was examined by rhinoscopy. RESULTS: A single treatment with Nasya/Prevalin led to a significant reduction of TNSS at 60, 75 and 90 min after dust mite allergen challenge as compared with placebo (pVCAS = 0.021, pVCAS = 0.035, pVCAS = 0.036, respectively). Mucosa changes assessed by the rhinoscopic score (on swelling, secretion and colour) were significantly worse in the placebo group compared with the Nasya/Prevalin group (P = 0.033). Nasya/Prevalin was well tolerated, and the safety was comparable with placebo. CONCLUSIONS: Treatment with Nasya/Prevalin was effective in preventing allergic reactions induced by dust mite allergen challenge.

Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body's defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects.

PURPOSE: The effect of brewers' yeast (1,3)-(1,6)-beta-D-glucan consumption on the number of common cold episodes in healthy subject was investigated. METHODS: In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-D-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. RESULTS: In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25% as compared to placebo (p = 0.041). The mean symptom score was 15% lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). CONCLUSION: The present study demonstrated that yeast beta-glucan preparation increased the body's potential to defend against invading pathogens.

The genome of the kinetoplastid parasite, Leishmania major.

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.