TOTUM-63, a plant-based polyphenol-rich extract, improves glycaemic control in subjects with prediabetes or early stage newly-diagnosed type 2 diabetes in a randomized, double-blind, placebo-controlled trial.

AIM: The plant-based polyphenol-rich extract TOTUM-63 improves glucose homeostasis in various preclinical models of obesity and type 2 diabetes (T2D). A pilot exploratory study showed that TOTUM-63 has good safety and tolerability profiles, and beneficial effects on postprandial glucose control in healthy individuals with overweight. The aim of this study was to assess the effects of TOTUM-63 on glycaemic control in individuals with prediabetes or early stage newly-diagnosed T2D (which does not require pharmacological treatment). MATERIALS AND METHODS: This study was a multicentre, randomized, double-blind, placebo-controlled trial. Individuals with prediabetes or early stage newly-diagnosed T2D and with overweight/abdominal obesity received TOTUM-63 (5 g/day) or placebo for 6 months. The primary outcome was the change in fasting blood glucose. RESULTS: Fifty-one participants (age: 57.1 ± 10 years; body mass index: 31.3 ± 5.7 kg.m2 ; 35 women and 16 men) completed the study (n = 38 TOTUM-63, n = 13 placebo). After 6 months, blood glucose concentration after fasting and after the 2-h oral glucose tolerance test was reduced in the TOTUM-63-treated group compared with the placebo group (placebo-corrected difference between baseline and month 6: -0.71 mmol/L, p < .05, and -1.93 mmol/L, p < .05, respectively). TOTUM-63 was safe and well tolerated and significantly reduced body weight gain (-1.9 kg; p < .05), waist circumference (-4.5 cm; p < .001), circulating triglycerides (-0.54 mmol/L; p < .01) and low-density lipoprotein-cholesterol (-0.38 mmol/L; p < .05) compared with placebo. CONCLUSIONS: TOTUM-63 lowered fasting blood glucose in participants with impaired fasting glycaemia and glucose intolerance. Moreover, TOTUM-63 showed a good safety and tolerability profile and improved several metabolic syndrome features. Therefore, TOTUM-63 is a promising candidate for T2D prevention.

Effects of Totum-63 on glucose homeostasis and postprandial glycemia: a translational study.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study.

BACKGROUND: Bacillus probiotics health benefits have been until now quite poorly studied in the elderly population. This study aimed to assess the effects of Bacillus subtilis CU1 consumption on immune stimulation and resistance to common infectious disease (CID) episodes in healthy free-living seniors. RESULTS: One hundred subjects aged 60-74 were included in this randomized, double-blind, placebo-controlled, parallel-arms study. Subjects consumed either the placebo or the probiotic (2.10(9) B. subtilis CU1 spores daily) by short periodical courses of 10 days intermittently, alternating 18-day course of break. This scheme was repeated 4 times during the study. Symptoms of gastrointestinal and upper/lower respiratory tract infections were recorded daily by the subjects throughout the study (4 months). Blood, saliva and stool samples were collected in a predefined subset of the first forty-four subjects enrolled in the study. B. subtilis CU1 supplementation did not statistically significantly decrease the mean number of days of reported CID symptoms over the 4-month of study (probiotic group: 5.1 (7.0) d, placebo group: 6.6 (7.3) d, P = 0.2015). However, in the subset of forty-four randomized subjects providing biological samples, we showed that consumption of B. subtilis CU1 significantly increased fecal and salivary secretory IgA concentrations compared to the placebo. A post-hoc analysis on this subset showed a decreased frequency of respiratory infections in the probiotc group compared to the placebo group. CONCLUSION: Taken together, our study provides evidence that B. subtilis CU1 supplementation during the winter period may be a safe effective way to stimulate immune responses in elderly subjects.

Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study.

PURPOSE: To determine the effect of 4 weeks of supplementation, then, withdrawal of a dietary supplement (DS) containing red yeast rice extract, policosanol and artichoke leaf extract at twice the recommended daily dose (6 tablets, 6-TAB) compared to the usual dose (3-TAB) or to a placebo (PLA), on blood lipid profiles and safety biomarkers. METHODS: Forty-five healthy subjects (15 per group), with untreated hypercholesterolaemia, were included in this randomised, double-blind, placebo-controlled clinical trial. RESULTS: After 4 weeks of supplementation, LDL-C was significantly lower in 6-TAB (-0.21 g/l; 95 % CI -0.38 to -0.03 g/l; p = 0.0217) and 3-TAB (-0.25 g/l; 95 % CI -0.42 to -0.07 g/l; p = 0.0071) compared to PLA, although no difference in LDL-cholesterol was observed between the two groups, while no effect was seen on triacylglycerol and HDL-cholesterol. Four weeks after the end of supplementation, no difference in LDL-C was seen between the PLA group and the DS-treated groups. The muscle breakdown biomarkers, as well as biomarkers of liver and renal function, were altered by neither dose of the DS. Acute application of the DS on permeabilised skeletal muscle fibres of rats did not induce deleterious effects on mitochondrial function. CONCLUSIONS: Supplementation with twice the recommended dose of the DS was effective in reducing LDL-cholesterol and appeared safe, but according to the present results, no additional benefit could be achieved compared to the recommended dose.

Effect of a high bicarbonate mineral water on fasting and postprandial lipemia in moderately hypercholesterolemic subjects: a pilot study.

BACKGROUND: During postprandial state, TG concentration is increasing and HDL cholesterol decreasing, leading to a transitory pro-atherosclerotic profile. Previous studies have reported that bicarbonate water improve postprandial lipemia. The objective of this study was to analyze the effect of a strongly bicarbonated mineral water on lipoprotein levels during fasting and postprandial state. METHODS: A controlled, randomised, double-blind cross-over design was conducted in 12 moderately hypercholesterolemic subjects after a daily ingestion of 1.25 L of mineral (SY) or low mineral water during eight weeks separated by a one week wash-out period. Blood samples were collected in first visit to the hospital (V1) before water consumption (referent or SY) and in a second visit (V2) after eight week water consumption period. The effect of the consumed water was studied in fasting and in postprandial state during ingestion of a meal and 0.5 L of water. RESULTS: Comparison of data between V1 and V2 after SY consumption showed a significant decrease in triglyceridemia (23%), VLDL TG (31%) and tendency to a decrease of VLDL cholesterol (p = 0.066) at fasting state. Whatever the consumed water during postprandial state, the measurement of total areas under curves did not show a significant difference. No difference was observed between SY and referent water consumption for measured parameters at fasting and postprandial state. CONCLUSION: When subjects consumed SY we showed a decrease of their basal TG and VLDLTG. The unexpected absence of effect of high mineralized water on postprandial lipemia, probably related to experimental conditions, is discussed in the discussion section.

A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial.

OBJECTIVE: To investigate the effect of a natural cholesterol-lowering supplement (NCLS) containing red yeast rice, policosanols and artichoke leaf extracts on blood lipid concentrations as well as on safety parameters when given over 16 weeks in 100 volunteers with untreated moderate hypercholesterolemia, in a randomized, double-blind, placebo-controlled trial. RESULTS: Reduction of primary outcome low-density lipoprotein cholesterol [-0.22 g/L (95% confidence interval, CI: -0.31 to -0.12) corresponding to -14.3% from baseline (95% CI: -21.5 to -7.2) compared to placebo], as well as total cholesterol, apolipoprotein B100 and apolipoprotein B100/apolipoprotein A-I ratio, were observed after 16 weeks of supplementation with NCLS. These effects were already observed at Week 4 and 10 of supplementation. No significant changes were observed in high-density lipoprotein, triacylglycerol, creatine kinase, lactate dehydrogenase and coenzyme Q10 levels, as well as in markers of liver and renal function. CONCLUSIONS: The NCLS was effective in reducing low-density lipoprotein cholesterol and apolipoprotein B100 in subjects with moderate hypercholesterolemia, without modifying safety parameters.

Circulating Human Metabolites Resulting from TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons from an Original Ex Vivo Clinical Trial.

TOTUM-070 is a patented polyphenol-rich blend of five different plant extracts showing separately a latent effect on lipid metabolism and potential synergistic properties. In this study, we investigated the health benefit of such a formula. Using a preclinical model of high fat diet, TOTUM-070 (3 g/kg of body weight) limited the HFD-induced hyperlipemia with a reduction in triglyceride (-32% after 6 weeks; -20.3% after 12 weeks) and non-HDL cholesterol levels (-21% after 6 weeks; -38.4% after 12 weeks). To further investigate such a benefit and its underlying mechanisms in humans, we designed an ex vivo clinical approach to collect the circulating bioactives resulting from TOTUM-070 ingestion and to determine their biological activities on human hepatocytes. Human serum was obtained from healthy subjects before and after intake of TOTUM-070 (4995 mg). The presence of circulating metabolites was assessed by UPLC-MS/MS. Serum containing metabolites was further incubated with hepatocytes cultured in a lipotoxic environment (palmitate, 250 µM). RNA sequencing analyses show that lipid metabolism was one of the most impacted processes. Using histologic, proteomic, and enzymatic assays, the effects of human TOTUM-070 bioactives on hepatocyte metabolism were characterized by (1) the inhibition of lipid storage, including both (2) triglycerides (-41%, p < 0.001) and (3) cholesterol (-50%, p < 0.001) intracellular content, (4) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity -44%, p < 0.001), and (5) a lowered fatty acid synthase protein level (p < 0.001). Altogether, these data support the beneficial impact of TOTUM-070 on lipid metabolism and provide new biochemical insights in human mechanisms occurring in liver cells.

Deep phenotyping and biomarkers of various dairy fat intakes in an 8-week randomized clinical trial and 2-year swine study.

Health effects of dairy fats (DF) are difficult to evaluate, as DF intakes are hard to assess epidemiologically and DF have heterogeneous compositions that influence biological responses. We set out to find biomarkers of DF intake and assess biological response to a summer DF diet (R2), a winter DF diet (R3), and a R3 supplemented with calcium (R4) compared to a plant-fat-based diet (R1) in a randomized clinical trial (n=173) and a 2-year study in mildly metabolically disturbed downsized pigs (n=32). Conventional clinical measures were completed by LC/MS plasma metabolomics/lipidomics. The measured effects were modeled as biological functions to facilitate interpretation. DF intakes in pigs specifically induced a U-shaped metabolic trajectory, reprogramming metabolism to close to its initial status after a one-year turnaround. Twelve lipid species repeatably predicted DF intakes in both pigs and humans (6.6% errors). More broadly, in pigs, quality of DF modulated the time-related biological response (R2: 30 regulated functions, primarily at 6 months; R3: 26 regulated functions, mostly at 6-12 months; R4: 43 regulated functions, mostly at 18 months). Despite this heterogeneity, 9 functions overlapped under all 3 DF diets in both studies, related to a restricted area of amino acids metabolism, cofactors, nucleotides and xenobiotic pathways and the microbiota. In conclusion, over the long-term, DF reprograms metabolism to close to its initial biological status in metabolically-disrupted pigs. Quality of the DF modulates its metabolic influence, although some effects were common to all DF. A resilient signature of DF consumption found in pigs was validated in humans.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

Short-term digestive tolerance of high-dose of NUTRIOSE®FB10 in adult.

NUTRIOSE®FB10 is a dextrin considered a dietary fiber. The present study aims to assess the digestive tolerance of a high dose of NUTRIOSE®FB10 consumed over the day, and its effect on digestive symptoms. In a randomized, double-blind, cross-over trial, 12 healthy men ingested 1 l/day orange juice containing 50 g either NUTRIOSE®FB10 or placebo (maltodextrin) in three equal doses at breakfast, lunch and 4:00 pm meal. Bloating, borborygmus, flatulence, nausea feelings, stomach ache, transit and stool consistency were evaluated at different times after the first consumption. Questionnaires on well-being and bowel movement were completed at 24 and 48 h. For all data except stool consistency, the area under the curve, the maximum score and the time of this maximum were calculated. For stool consistency, the mean score over 48 h was determined. There was no statistical difference between NUTRIOSE®FB10 and placebo on each criterion. NUTRIOSE®FB10 is well tolerated during a single day at 50 g divided into three doses.

Effects of chicory inulin in constipated elderly people: a double-blind controlled trial.

The impact of the daily consumption of 15 g chicory native inulin on fecal levels of bifidobacteria, stool parameters and quality of life of elderly constipated volunteers was investigated in a randomized, double-blind, controlled versus placebo clinical trial. The impact of supplementation on constipation was assessed with questionnaires on bowel motor function parameters, visual analogue scales on bowel symptoms and quality of life. Fecal bacteria counts were determined at the beginning and at the end of the supplementation. Inulin supplementation led to a significant increase in total fecal bacteria (P < 0.01) and bifidobacteria (P < 0.001) concentrations after 28 days of consumption. Volunteers (n = 25) in the inulin group reported increased satisfaction about digestion (P < 0.01) and reduced defecation difficulties (P < 0.001) during the supplementation. Slight gastrointestinal symptoms (flatulence) were reported but did not lead to discontinuation. Daily supplementation with 15 g inulin improves constipation and quality of life in an elderly population with constipation.

Short-term digestive tolerance of chocolate formulated with maltitol in children.

INTRODUCTION: Polyols are molecules of interest for food industries because of their technological and nutritional properties. Maltitol is known for its non-acidogenic and low-energetic properties. Our primary objective was to evaluate the digestive tolerance of maltitol in children. The secondary objective was to compare the organoleptic properties of maltitol and sucrose in chocolate. METHOD: Healthy children were included in a double-blind, randomized parallel study versus placebo. The subjects received one dose of either maltitol or sucrose chocolate per week. Increasing doses were tested from 5 to 15 g maltitol in chocolate. Abdominal pain, rumbling, bloating and flatulence scores were evaluated using visual analog scales. RESULTS: Some statistical differences on intestinal parameters were observed in the maltitol group compared with placebo, mainly concerning flatulence scores. Nevertheless, these scores remained low and could be considered minor. CONCLUSION: Our results suggest that maltitol was well tolerated in children at 15 g in one intake.

Effect of milk fat on LDL cholesterol and other cardiovascular risk markers in healthy humans: the INNOVALAIT project.

BACKGROUND: Milk has a specific saturated fatty acid profile and its calcium content may change the kinetics of fat absorption. OBJECTIVE: The goal of this study was to compare the effect on LDL Cholesterol and other risk markers of four isolipidic diets differing by their fat food source, vegetable fat, spring milk fat, winter milk fat or winter milk fat supplemented with calcium, in healthy moderately hypercholesterolemic humans. INDIVIDUALS AND METHODS: This double-blind, randomized trial with four parallel arms included 172 healthy adults with plasma LDL cholesterol (LDL-C) from 130 to 220 mg/dL and triglycerides below 300 mg/dL. Individual meal plans ensured a stable energy intake. In the three diets containing milk fat, milk fat provided 38% of energy. Vegetable fat and spring milk fat diets provided the same amount of saturated fatty acids while the winter milk fat diets were slightly richer in saturated fatty acids. Vegetable fat diet and winter milk fat diets provided the same amount of palmitic acid (7.0% EI), while the spring milk fat diet was slightly poorer in this fatty acid (5.1% EI). Cardiovascular risk markers were analyzed after 8 weeks of dietary intervention. RESULTS: There was no significant difference in LDL-C and other markers, except total cholesterol (TC), apo C3 and CRP. TC was significantly higher with spring milk fat than with vegetable fat. CONCLUSIONS: In this trial, the chosen vegetable fat did not have a significant beneficial effect on LDL-C compared to dairy fat. However, sub-group analysis showed differences in TC, apo C3 and CRP. These results need confirmation and long-term studies aiming at cardiovascular endpoints are warranted.

Glycemic Index and Insulinemic Index of Foods: An Interlaboratory Study Using the ISO 2010 Method.

An official method for determining food glycemic index (GI) was published by the Organization for International Standardization (ISO) in 2010, but its performance has not been assessed. Therefore, we aimed to determine the intra- and inter-laboratory variation of food GI values measured using the 2010 ISO method. Three laboratories (Australia, Canada and France) determined the GI and insulinemic-index (II) of six foods in groups of 13-15 participants using the 2010 ISO method and intra- and inter-laboratory Standard Deviations (SDs) were calculated. Overall mean food GIs varied from 47 to 86 (p < 0.0001) with no significant difference among labs (p = 0.57) and no food × laboratory interaction (p = 0.20). Within-laboratory SD was similar among foods (range, 17.8-22.5; p = 0.49) but varied among laboratories (range 17.5-23.1; p = 0.047). Between-laboratory SD of mean food GI values ranged from 1.6 to 6.7 (mean, 5.1). Mean glucose and insulin responses varied among foods (p < 0.001) with insulin (p = 0.0037), but not glucose (p = 0.054), varying significantly among labs. Mean II varied among foods (p < 0.001) but not among labs (p = 0.94). In conclusion, we found that using the 2010 ISO method, the mean between-laboratory SD of GI was 5.1. This suggests that the ISO method is sufficiently precise to distinguish a mean GI = 55 from a mean GI ≥ 70 with 97-99% probability.

Measuring the glycemic index of foods: interlaboratory study.

BACKGROUND: Many laboratories offer glycemic index (GI) services. OBJECTIVE: We assessed the performance of the method used to measure GI. DESIGN: The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally. RESULTS: Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model). CONCLUSIONS: The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.

Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia.

BACKGROUND: Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects. METHODS: In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents) or without plant sterols (control) for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C). Secondary measurements were changes in total cholesterol (TC), non-HDL cholesterol (non-HDL-C), HDL cholesterol (HDL-C) and triglycerides. RESULTS: Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p < 0.05). TC and non-HDL-C concentrations decreased by 0.26 mmol/l and 0.31 mmol/l (each p < 0.05), respectively. Mean reductions in total, LDL and non-HDL cholesterol were significantly greater than in the placebo group (p < 0.05). HDL-C and triglycerides were not affected. Compliance was very high (>96%), and products were well tolerated. CONCLUSION: Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.

Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis.

AIM: To confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management. METHODS: An individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline ("IBS-C ≥ 2 subpopulation"). RESULTS: S. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as "normal" compared to Placebo (respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation (Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009). CONCLUSION: This meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations.

Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and/or discomfort. Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear. OBJECTIVE: This study was designed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms. METHODS: A randomized, double blind, placebo-controlled trial has been performed in 379 subjects with diagnosed IBS. Subjects were randomly supplemented with the probiotics (1000 mg) or placebo for 12 weeks. Questionnaires (gastrointestinal symptoms, stools, wellbeing, and quality of life) were completed. Primary endpoint was percentage of responders defined as having a 50% decrease in the weekly average "intestinal pain/discomfort score" for at least 4 out of the last 8 weeks of the study. RESULTS: There was no overall benefit of S. cerevisiae I-3856 on IBS symptoms and wellbeing in the study population. Moreover, S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects (p > 0.05). Planned subgroup analyses showed significant effect in the IBS-C subjects: improvement of gastrointestinal symptoms was significantly higher in active group, compared to placebo, on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation. CONCLUSIONS: In this study, S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients. However, it seems to have an effect in the subgroup with constipation which needs further studies to confirm (NCT01613456 in ClinicalTrials.gov registry).

A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome.

BACKGROUND: We aimed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae in a randomized double-blind placebo-controlled clinical trial. METHODS: Overall, 179 adults with irritable bowel syndrome (Rome III criteria) were randomized to receive once daily 500 mg of Saccharomyces cerevisiae, delivered by one capsule (n = 86, F: 84%, age: 42.5 ± 12.5), or placebo (n = 93, F: 88%, age: 45.4 ± 14) for 8 weeks followed by a 3-week washout period. After a 2-week run-in period, cardinal symptoms (abdominal pain/discomfort, bloating/distension, bowel movement difficulty) and changes in stool frequency and consistency were recorded daily and assessed each week. A safety assessment was carried out throughout the study. RESULTS: The proportion of responders, defined by an improvement of abdominal pain/discomfort, was significantly higher (p = 0.04) in the treated group than the placebo group (63% vs 47%, OR = 1.88, 95%, CI: 0.99-3.57) in the last 4 weeks of treatment. A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms. Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency. CONCLUSION: Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification. Thus, Saccharomyces cerevisiae may be a new promising candidate for improving abdominal pain in subjects with irritable bowel syndrome.

Digestive absorption of silicon, supplemented as orthosilicic acid-vanillin complex.

SCOPE: Silicon (Si) is an abundant element on earth. It is found naturally in water in the form of orthosilicic acid (OSA), however this form is not stable under certain conditions such as in highly concentrated and non-neutral pH solutions, which lead to its polymerization and reduced bioavailability. This study aimed to assess the bioavailability of Si from OSA stabilized by vanillin (OSA-VC). METHODS AND RESULTS: This was a single-center, double-blind, cross-over randomized controlled trial. Fourteen healthy subjects were recruited and consumed either OSA-VC or a placebo on two separate occasions. Blood and urine samples were collected during 6 h following ingestion and analyzed to determine Si absorption and excretion. Plasma Si area under the curve (0-6 h) was significantly higher after OSA-VC ingestion compared to placebo ingestion (p = 0.0002). Significantly higher urinary Si excretion was also reported over the 6-h period after OSA-VC ingestion compared to placebo (p<0.0001). Approximately 21% of ingested Si was excreted in urine during this period. CONCLUSION: Although many studies have investigated the metabolism and bioavailability of Si supplemented in foods or as a food ingredient, this was the first to investigate and demonstrate the digestibility of OSA administered in a complex form with vanillin.