Phase 1 Study of the Pharmacology of BTI320 Before High-Glycemic Meals.

BTI320 is a proprietary fractionated mannan polysaccharide being studied for attenuation of postprandial glucose excursion. The apparent blood glucose-lowering effect of this compound is effective in lowering postprandial hyperinsulinemia, participating in the metabolic regulation of other lipid molecules; the consequence of this activity is yet to be validated with BTI320 with respect to the risk of cardiovascular disease. The primary objective of the study was to determine the postprandial glucose and insulin responses to 3 test meals containing rice alone or consumed with BTI320 (study A) or 3 test meals (SpriteTM ) alone or consumed with BTI320 (study B). Twenty overweight but otherwise healthy volunteers, 4 female and 6 male (mean age 29 years, BMI 27-28 kg/m2 ) in study A and 6 female and 4 male (mean age 32 years, BMI 25-32 kg/m2 ) in study B participated in the BTI320 evaluations. Standardized postprandial response methodology was utilized. In study A the addition of 6- and 12-g BTI320 tablets reduced postprandial glucose responses to white rice by 19% and 32% and reduced postprandial insulin responses by 16% and 24%, respectively (P ≤ .05). In study B 2.6 and 5.2 g BTI320 reduced the glycemic index by 10% and 14%, respectively, and led to 14% and 18% decreases in the insulinemic index of the soft drink (P ≤ .05). These 2 studies demonstrated that the consumption of BTI320 before carbohydrate food or sugary beverage significantly reduced postprandial glucose levels and insulin responses to that meal or beverage in a dose-dependent manner.

A glucogalactomannan isolated from Agaricus bisporus induces apoptosis in macrophages through the JNK/Bim/caspase 3 pathway.

Agaricus bisporus is one of the most important edible and medicinal mushrooms in the world. It has been well known that Agaricus bisporus has an immunoregulatory role, but its active ingredients have not been completely identified. In this study, a glucogalactomannan named TJ3 was isolated and purified from Agaricus bisporus. TJ3 (827 kDa) is composed of mannose, galactose, glucose and xylose in the ratio 28.26 : 27.82 : 20.88 : 9.87 mainly joined by ß-linkages. Functional analysis of TJ3 revealed that it effectively induced apoptosis in RAW 264.7 cells, a mouse macrophage cell line. Cell apoptosis was determined by an Annexin V/PI staining assay. After treatment with TJ3 (2 µg mL-1) for 16 h, apoptosis was observed in 34% of the Raw cells (9% in the non-treated control cells). TJ3 treatment remarkably increased the production of cleaved caspase-3, PARP and Bim, and decreased the level of Bcl-2 although no obvious change in the level of Bax was observed. Interestingly, further elucidation of the molecular mechanism underlying the role of TJ3 in the induction of apoptosis showed that TJ3 activated the JNK signaling pathway through TLR4 and subsequently promoted the expression of Bim and activation of caspase-3. Our results demonstrate that TJ3 may be a novel active component in Agaricus bisporus responsible for its immunoregulatory role by the induction of macrophage apoptosis.

Galactomannan More than Pectin Exacerbates Liver Injury in Mice Fed with High-Fat, High-Cholesterol Diet.

SCOPE: Galactomannan and citrus pectin are considered 'super fibers' known for altering gut microbiota composition and improving glucose and lipid metabolism. The study aims to investigate the fiber's effect on a nonalcoholic steatohepatitis (NASH) model. METHODS AND RESULTS: Two feeding experiments are carried out using groups of 7-8 week-old male C57BL/6J mice. The diets used are based on a high cholesterol/cholate diet (HCD), such as a nutritional NASH model. Mice are fed a diet with or without 15% fiber-citrus pectin (HCD-CP) or galactomannan (HCD-G) together with the HCD (first experiment), which commenced 3 weeks prior to the HCD (second experiment). Liver damage is evaluated by histological and biochemical parameters. Galactomannan leads to lesser weight gain and improved glucose tolerance, but increased liver damage. This is shown by elevated levels of liver enzymes compared to that with HCD alone. Fibers induce higher steatosis, as evaluated by liver histology. This intriguing result is linked to various changes in the gut microbiota, such as elevated Proteobacteria levels in the galactomannan group, which are correlated with disturbed metabolism and dysbiosis. CONCLUSIONS: In a NASH mouse model, galactomannan increases liver damage but improves glucose metabolism. Changes in the microbiota composition may answer this enigmatic observation.

Safety considerations of plant polysaccharides for food use: a case study on phenolic-rich softwood galactoglucomannan extract.

A growing population and concern over the sufficiency of natural resources for feeding this population have motivated researchers and industries to search for alternative and complementary sources of food ingredients and additives. Numerous plant species and parts of plants are explored as raw materials for food production. An interesting example is wood; to date, only a few wood-based additives or ingredients are authorized for food use. Wood hemicelluloses, such as softwood galactoglucomannans (GGM), constitute an abundant bioresource that shows a high potential functionality in edible materials. Spruce GGM acts as a multi-functional emulsion stabilizer, and it could be used in various processed food products, replacing less effective, conventional emulsifiers. Before new materials can be released into the food market, their safety must be evaluated, according to the Novel Food regulation. This review focuses on the safety aspects that must be considered before polysaccharide- and phenolic-rich plant extracts can be awarded the status of authorized food ingredients. In this review, GGM is presented as a case study and examples are given of plant-based polysaccharides that are already authorized for food purposes. The legislation regarding Novel Food ingredients in Europe is also briefly reviewed.

Development and preclinical evaluation of a new galactomannan-based dressing with antioxidant properties for wound healing.

We describe a novel wound dressing (HR006) with two components: a lyophilized matrix of the galactomannan from locust bean gum (LBG) and an antioxidant hydration solution (AHsol) containing curcumin and N-acetyl-L-cysteine (NAC). Physico-structural analyses of the LBG matrix revealed homogeneous interconnected pores with high absorbing capacity showing excellent properties for moist wound care (MWC). In an in vitro oxidative stress fibroblast injury model, the AHsol showed relevant protective effects reducing intracellular reactive oxygen species (ROS) production, rescuing cell viability, and regulating expression of inflammation-related genes (COX-2, TNF-α, IL-1α, IL-1ß). The new dressing showed good biocompatibility profile as demonstrated by cytotoxicity, hemocompatibility, and skin irritation tests. Moreover, in an in vivo skin wound model in pigs, this dressing enhanced the production of healthy and organized granulation tissue and re-epithelization. In summary, HR006 exhibits significant antioxidant activity, good biocompatibility, and excellent repair capabilities improving tissue remodeling and the healing of wounds.

Partially hydrolyzed guar gum accelerates colonic transit time and improves symptoms in adults with chronic constipation.

BACKGROUND AND AIM: Partially hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling dietary fiber with a wide range of uses in clinical nutrition. The aim of this prospective study was to investigate the effect of guar gum on colonic transit time (CTT) and symptoms of chronic constipation. METHODS: We enrolled patients fulfilling Rome III criteria for chronic constipation. CTT was measured before and at the end of treatment. After a 2-week run-in period, patients received 5 mg PHGG daily for 4 weeks. During study period, patients kept daily symptoms, stool and laxative usage diaries. They also recorded their symptom-related satisfaction weekly and treatment adverse events. RESULTS: Forty-nine patients received treatment; 39 (80 %) completed the study. Treatment significantly reduced colon transit time, from 57.28 ± 39.25 to 45.63 ± 37.27 h (p = 0.026), a reduction more prominent in slow transit patients (from 85.50 ± 27.75 to 63.65 ± 38.11 h, p = 0.016). Overall, the weekly number of complete spontaneous and spontaneous bowel movements increased significantly (p < 0.001); the latter correlated significantly with the acceleration of CTT in the overall population and in slow transit patients (B = 0.382; p = 0.016 and B = 0.483; p = 0.023, respectively). In addition, the number of bowel movements with straining decreased (p < 0.001) and stool form improved (p < 0.001), while days with laxative intake and days with abdominal pain decreased (p = 0.001 and p = 0.027, respectively). CONCLUSION: Four-week PHGG use accelerates colon transit time in patients with chronic constipation, especially in those with slow transit, and improves many of their symptoms including frequency of bowel movements.

Safety and efficacy of the nonsystemic chewable complex carbohydrate dietary supplement PAZ320 on postprandial glycemia when added to oral agents or insulin in patients with type 2 diabetes mellitus.

OBJECTIVE: Our primary objective was to evaluate the effect of the dietary supplement PAZ320 on postprandial glucose excursion. PAZ320 is derived from glucomannan and acts by blocking carbohydrate hydrolyzing enzymes and by binding to ingested polysaccharides. Endpoints included area under the curve during postprandial glucose excursion (gAUC) and adverse reactions. METHODS: In an open-label, sequential dose-escalation, prospective study, we examined the efficacy and safety of PAZ320 in 24 subjects with type 2 diabetes treated with oral agents and/or insulin. Subjects consumed 75 g jasmine rice alone or with low-dose (8 g) or high-dose (16 g) PAZ320. A real-time blinded continuous glucose monitor (CGM) was used to assess 3-hour postprandial glycemia. RESULTS: We found that 45% of subjects responded to high-dose PAZ320 as evidenced by a decrease in gAUC of 40% compared to baseline in a dose-dependent manner. The effect of PAZ320 does not correlate with duration of diabetes and seems to work regardless of concurrent diabetes medications. The responders had higher postmeal glucose elevation at baseline, while the nonresponders showed no effect or paradoxic glucose response to PAZ320. There was no severe hypoglycemia, and the gastrointestinal side effects were mild. CONCLUSIONS: PAZ320 may be useful as an adjunct to decrease postprandial glycemia in type 2 diabetes, although patients should verify its effect on postprandial glucose due to a possible paradoxic response. Its safety profile is reassuring. Further study is required to determine its long-term effects on glycated hemoglobin (HbA1c) and to further define which subpopulation may respond to PAZ320.

The effect of an aloe polymannose multinutrient complex on cognitive and immune functioning in Alzheimer's disease.

Alzheimer's disease (AD) is a leading killer of Americans, imparts a significant toll on the quality of life of the patient and primary caregiver, and results in inordinate costs in an already overburdened medical system. Prior studies on cholinesterase inhibitors among AD patients have shown minimal amelioration of disease symptoms and/or restoration of lost cognitive functioning. The effect of improved nutrition, particularly with dietary supplements, on cognitive functioning may offer an alternative strategy compared to standard treatment. The present pilot study investigated the effect of an aloe polymannose multinutrient complex (APMC) formula on cognitive and immune functioning over 12 months among adults diagnosed with AD. Subjects participated in an open-label trial and consumed 4 teaspoons per day of the APMC. The ADAS-cog, MMSE, ADCS-ADL, and SIB were administered at baseline and 3, 6, 9, and 12 months follow-up. Cytokines and lymphocyte and monocyte subsets were assessed at baseline and 12 months. The mean ADAS-cog cognition score significantly improved at 9 and 12 months from baseline, and 46% of our sample showed clinically-significant improvement (≥4-point change) from baseline to 12 months. Participants showed significant decreases in tumor necrosis factor-α, vascular endothelial growth factor, and interleukins-2 and-4. CD90+, CD95+CD3+, CD95+CD34+, CD95+CD90+, CD14+CD34+, CD14+CD90+, and CD14+CD95+ decreased significantly, whereas CD14+ significantly increased. Participants tolerated the APMC supplement with few, temporary adverse reactions. Our results showed improvements in both clinical and physiological outcomes for a disease that otherwise has no standard ameliorative remedy.

Acemannan, a polysaccharide extracted from Aloe vera, is effective in the treatment of oral aphthous ulceration.

OBJECTIVES: The objective of this study was to elucidate the safety and effectiveness of acemannan, a polysaccharide extracted from Aloe vera, in the treatment of oral aphthous ulceration. DESIGN: A skin patch test was performed on 100 healthy subjects, and 0.5% acemannan in Carbopol® 934P NF (Lubrizol Corporation, USA) was applied to the oral mucosa of the lower lip of 50 healthy participants 3 times/day for 7 days. Oral examinations and blood tests measuring liver and kidney function were performed prior to, and following, 7 days of application to assess the side-effects of acemannan when used on oral mucosa. Another 180 subjects with recurrent aphthous ulceration randomly received one of three treatments: 0.1% triamcinolone acetonide (HOE Pharmaceuticals, Malaysia), 0.5% acemannan in Carbopol® 934P NF, or pure Carbopol® 934P NF. Medications were applied to the ulcers 3 times/day for 7 days. Measurements of ulcer size and patient satisfaction ratings were performed on days 2, 5, and 7. Pain ratings were recorded daily. RESULTS: No subjects exhibited allergic reactions or side-effects to acemannan. There were no significant differences between the blood test values before and after 7 days of acemannan application. The effectiveness of acemannan in reducing ulcer size and pain was superior to that of control, but inferior to that of 0.1% triamcinolone acetonide. Patients were mostly satisfied with 0.1% triamcinolone acetonide and acemannan treatment. CONCLUSIONS: Acemannan can be used for the treatment of oral aphthous ulceration in patients who wish to avoid the use of steroid medication, although the effectiveness was not comparable to that of 0.1% triamcinolone acetonide.

Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women.

INTRODUCTION: Prebiotics positively affect gut microbiota composition, thus improving gut function. These properties may be useful for the treatment of constipation. OBJECTIVES: This study assessed the tolerance and effectiveness of a prebiotic inulin/partially hydrolyzed guar gum mixture (I-PHGG) for the treatment of constipation in females, as well as its influence on the composition of intestinal microbiota and production of short chain fatty acids. METHODS: Our study enrolled 60 constipated female health worker volunteers. Participants reported less than 3 bowel movements per week. Volunteers were randomized to treatment with prebiotic or placebo. Treatment consisted of 3 weeks supplementation with 15 g/d IPHGG (fiber group) or maltodextrin (placebo group). Abdominal discomfort, flatulence, stool consistency, and bowel movements were evaluated by a recorded daily questionnaire and a weekly interview. Changes in fecal bacterial population and short chain fatty acids were assessed by real-time PCR and gas chromatography, respectively. RESULTS: There was an increased frequency of weekly bowel movements and patient satisfaction in both the fiber and placebo groups with no significant differences. Total Clostridium sp significantly decreased in the fiber group (p = 0.046) and increased in the placebo group (p = 0.047). There were no changes in fecal short chain fatty acid profile. CONCLUSIONS: Consumption of I-PHGG produced clinical results comparable to placebo in constipated females, but had additional protective effects on gut microbiota by decreasing the amount of pathological bacteria of the Clostridium genera.

Aloe vera as a functional ingredient in foods.

The main scientific discoveries on Aloe vera published mainly in the last three decades are presented in this work. After describing Aloe from a botanical point of view, the papers related with the chemical composition of different parts of the leaf of Aloe, particularly those in which the gel is described and are presented in a synthetic manner. The chemical analyses reveal that Aloe gel contains mannose polymers with some glucose and other sugars, among which the most important is Acemannan. Besides these, other components such as glycoproteins, enzymes, amino acids, vitamins, and minerals are described. Different factors also affecting the chemical composition of the gel, such as species and variety, climatic and soil conditions, cultivation methods, processing and preservation, are enumerated and discussed. On the other hand, the main therapeutic applications have been revised and the possible damaging effects of Aloe are also commented upon. A special emphasis is placed on the biologically active compounds or groups of compounds responsible for the therapeutic applications and which are their action mechanisms. The paper concludes that more research is needed to confirm the therapeutic and beneficial effects and to definitively clarify the myth surrounding Aloe vera. A general view on the problem of the commercialization and establishment of the quality and safety of Aloe products in the food industry has been offered here. The main points and European regulations that need to be considered regarding the quality control of prepared Aloe products are presented in this paper.

Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial.

In the setting of a six-month, open-label clinical trial, 141 consecutively enrolled, hypertensive, overweight patients were randomized to the oral ingestion of psyllium powder or guar gum 3.5 gr t.i.d., to be taken 20 min before the main two meals, or to standard diet. Both fibers improved significantly BMI, FPG, FPI, HOMA Index, HbA1c, LDL-C, and ApoB. Psyllium supplementation only exerted a significant improvement in plasma TG concentration, in SBP and DBP. In our study, six-month supplementation with psyllium fiber, but not with guar fiber nor standard diet, appears to significantly reduce both SBP and DBP in hypertensive overweight subjects.

Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran .

We report the preclinical testing of a synthetic receptor-binding macromolecule, [(99m)Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K(D) = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [(99m)Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 +/- 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10(-2) mSv/MBq. This preclinical study demonstrates that [(99m)Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.

Partially hydrolyzed guar gum: clinical nutrition uses.

OBJECTIVE: This paper provides a review of research on partially hydrolyzed guar gum that is relevant to clinical nutrition practice. METHODS: All relevant papers published on partially hydrolyzed guar gum were reviewed and the results summarized. RESULTS: Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber with a wide range of uses in clinical nutrition. Its low viscosity allows its use in enteral products and beverages. PHGG can be added to enteral formulas and food products as a dietary fiber source. PHGG provides the benefits associated with dietary fiber ingestion. Addition of PHGG to the diet reduced laxative dependence in a nursing home population. PHGG also reduced the incidence of diarrhea in septic patients receiving total enteral nutrition and reduced symptoms of irritable bowel syndrome. PHGG also increased production of Bifidobacterium in the gut. CONCLUSION: The ease of use of PHGG and its clinical effectiveness make it a good choice in clinical nutrition practice.

A study to assess the effect of dietary supplementation with soluble fibre (Minolest) on lipid levels in normal subjects with hypercholesterolaemia.

Hypercholesterolaemia is one of the major risk factors in the development of coronary artery disease. In recent years, many nonprescription treatments have become available for cholesterol lowering. Minolest is a product that contains guar gum and psyllium as the principal active ingredients. We conducted a randomised, placebo-controlled, double-blind, parallel-group study to assess the efficacy of Minolest as a lipid-lowering agent. Secondary aims included assessment of the effect on blood pressure and obesity. We also looked at the acceptability of the product and side effects associated with its ingestion. After a 4-week run-in period, 83 subjects were randomised to receive placebo or Minolest (16.5 g/day) for 3 months. Seven subjects defaulted follow up, 5 in the placebo group and 2 in the active treatment group. In addition, 9 subjects (5 on active treatment and 4 on placebo) had total cholesterol fall into the optimal range (< 5.2 mmol/l) during the run-in phase and were removed from the study. At baseline in the active treatment group, total cholesterol was 6.1 (5.43 to 8.06) mmol/l, triglyceride 1.54 (0.56 to 4.19) mmol/l, HDL cholesterol 1.32 +/- 0.43 mmol/l and LDL cholesterol 4.1 (3.10 to 6.27) mmol/l. In the placebo group, total cholesterol was 5.84 (5.32 to 8.38) mmol/l, triglyceride 1.47 (0.69 to 11.0) mmol/l, HDL cholesterol 1.15 +/- 0.33 mmol/l and LDL cholesterol 3.87 (2.46 to 5.14) mmol/l. The differences in the baseline characteristics were not statistically significant except the LDL-cholesterol. Minolest produced a 3.24% (SD = 7.85%, P = 0.020) decrease in total cholesterol and 5.45% decrease in LDL cholesterol (SD = 10.25%, P = 0.0034) but no significant difference in serum triglyceride, weight, body mass index or blood pressure. This was not seen in the placebo group. The percentage fall in LDL cholesterol increased to 7.16% and 7.37% in subjects who consumed at least 50% and 70% of the treatment respectively. There were few side effects. The authors conclude that this product has a small impact on the lipid profile and may be useful only in subjects with mild hypercholesterolaemia and a low risk of coronary artery disease.

Long-term animal feeding trial of the refined konjac meal. I. Effects of the refined konjac meal on the calcium and phosphorus metabolism and the bone in rat.

Effects of refined konjac meal (RKM) on the calcium and phosphorus metabolism and bone parameters were observed in rats of both sexes fed with food containing 1% of RKM for 18 months. A comparable group of rats fed on basic diet only was used as a control. Results obtained indicate that all the measured parameters (serum calcium and phosphorus level, femur weight and its calcium and phosphorus content, and the osteometry of the tibia) showed no significant difference between the experimental and the control groups. Thus there is no adverse effect either on the calcium and phosphorus metabolism or on the bone after a long-term intake at a moderate dosage.

Modification in sucrose tolerance test with acarbose, guargum and their combination in patients with non-insulin dependent diabetes.

The study was undertaken to assess the efficacy guargum, Acarbose and their combination in modifying the sucrose absorption in patients of non Insulin dependent diabetes mellitus (NIDDM). Fifty patients of NIDDM were randomly distributed in three groups. Group A had 20 patients who received 20 grams of guargum, Group B had 10 patients who received 100 mg of Acrabose, Group C had 20 patients who received 10 grams of guargum and 50 grams of Acrabose. All the patients underwent 50 grams sucrose tolerance test with and without the trial drugs. Blood glucose levels were determined at 0, 30, 60, 90 and 120 minutes after sucrose loading. With the drugs, there was a significant decrease in the blood glucose levels at all time intervals (p < 001) in all the three groups. In all the three groups the blood glucose levels with the trial drugs was significantly lower (p < 001) than without the drug. It was seen that acarbose alone and guargum alone did not differ significantly in reducing the blood sugar level whereas combination of two produced significantly greater reduction in blood glucose levels than either of the drug used alone. Thus both guargum and acarbose are equally effective in modifying the absorption of sucrose. When combined in half the dosage they have synergistic effect and the reduction in blood glucose level is greater than either of the drug used alone.

The rachitogenic effects of fractions of rye and certain polysaccharides.

When fed to chicks rye is rachitogenic as well as growth depressing. The component or components of rye that cause these effects have not been identified. In an attempt to separate the factors, a water extract of rye was fractionated by precipitation with ethanol or ammonium sulfate. The precipitated fractions were fed to chicks. Although there were different responses to growth and bone ash from the ethanol fractions, they were not statistically significant. In another experiment, guar gum, pectin, or gum arabic was fed to chicks as 2% of the diet. Guar gum was both growth depressing and rachitogenic, pectin was only growth depressing, and gum arabic was without effect.