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Clinical Studies
References
Beta Glucans may be beneficial in hypercholesterolemia, diabetes, cancer and HIV/AIDS. Beta Glucans are also used orally as an immunostimulant in people with conditions that may compromise their immune system such as chronic fatigue syndrome, physical and emotional stress and patients receiving chemotherapy or radiation treatment. It is also used orally for colds (common cold), flu (influenza), allergies, hepatitis, Lyme disease, asthma, ear infections, aging, ulcerative colitis and Crohn's disease, fibromyalgia, rheumatoid arthritis and multiple sclerosis.
Beta Glucans are polysaccharides and primary components in cell walls of bacteria, fungi (such as Lentinus edodes and Grifola frondosa), yeasts, algae, lichens and plants such as oats and barley, or are excreted extracellularly by various fungi which cannot digest and absorb Beta Glucans because they lack the enzyme beta-1-3-glucanase needed to break them down. Beta Glucans may have antibacterial, antiviral, antifungal, antiparasitic and antitumor activity, and have the ability to promote recovery from sepsis and immunosuppression associated with various disease states or conditions such as HIV infection or whole body radiation.
Beta Glucans also seem to have anticancer effects. They don't seem to have direct anti-tumor or antibacterial activity, but are thought to act as biological response modifiers (BRMs) that restore or enhance humoral and cell-mediated immune responses.
Beta Glucan is useful for wound healing after surgery and there is some evidence they can decrease inflammation and accelerate the repair of surgical wounds by stimulating macrophages and increasing macrophage infiltration, causing increased tissue granulation and enhanced re-epithelization of tissue. For hypercholesterolemia Beta Glucans are thought to lower cholesterol by forming a layer adjacent to the intestinal mucosa that prevents cholesterol).
Published Clinical Studiesclin
1
Sweeteners and beta-glucans improve metabolic and anthropometrics variables in well controlled type 2 diabetic patients.
Reyna NY, Cano C, Bermudez VJ, Medina MT, Souki AJ, Ambard M, Nunez M, Ferrer MA, Inglett GE.
Endocrine and Metabolic Research Center, Nutrition School, University of Zulia, Maracaibo, Venezuela. nadiareyna@hotmail.com
The introduction of fat and carbohydrates replacers has been a revolutionary advance in treating obesity and diabetes mellitus. Since these materials have shown to have beneficial effects on the metabolic profiles of diabetic patients, they should be useful in designing specific foods for patients with diabetes. OBJECTIVE: To compare metabolic and anthropometric improvements elicited by a diet based on the American Diabetic Association's nutrition recommendations with a modified, low-energy diet incorporating fat replacers and non-sucrose sweeteners. DESIGN: A total of 16 male, well controlled type 2 diabetes patients were divided into two groups of eight; one group received the diet based on the American Diabetic Association's nutrition recommendations, and the other was fed a modified, low-calorie diet containing a fat replacer (beta-glucans derived from oats) and the sweeteners, sucralose and fructose. Both groups were maintained on their respective diets for 4 weeks. All patients performed daily aerobic exercise consisting of walking for 60 minutes. Body weight, body mass index, basal glycemia, hemoglobin HbA1C, and lipid profile were determined in each patient before starting the diets and after 4 weeks of dietary intervention. RESULTS: Both diets produced significant improvements in weight, body mass index, lipid profile, basal glucose, and HbA1C. However, the experimental diet was superior to the American Diabetic Association's diet in improving metabolic and anthropometric profile: greater increase in HDL cholesterol and larger decreases in HbA1C, weight, and body mass index. CONCLUSIONS: A diet incorporating a fat replacer and non-sucrose sweeteners produced a greater improvement in metabolic and anthropometric variables in well controlled type 2 diabetic patients when compared with a diet based on American Diabetic Association's nutrition recommendations.
PMID: 14624282 [PubMed - in process]
Plasma lipid changes after supplementation with beta-glucan fiber from yeast.2
Nicolosi R, Bell SJ, Bistrian BR, Greenberg I, Forse RA, Blackburn GL.
Center for Cardiovascular Disease Control, University of Massachusetts-Lowell, USA.
BACKGROUND: Dietary fiber has been shown to improve blood lipids. OBJECTIVE: The purpose of this study was to evaluate the effect on serum lipids of a yeast-derived beta-glucan fiber in 15 free-living, obese, hypercholesterolemic men. DESIGN: After a 3-wk period in which subjects ate their usual diet, 15 g fiber/d was added to the diet for 8 wk and then stopped for 4 wk. Plasma lipids were measured weekly during baseline and at week 7 and 8 of fiber consumption, and again at week 12. RESULTS: Compared with baseline, fiber consumption significantly reduced plasma total cholesterol (by 8% at week 7 and 6% at week 8; P < 0.05 using Bonferroni correction); week 12 values did not differ from baseline. No significant differences were noted between baseline LDL cholesterol and values at weeks 7, 8, or 12 when comparing individual groups by using Bonferroni correction, even though the overall one-way analysis of variance with repeated measures was highly significant (P < 0.001). LDL-cholesterol concentrations did decline by 8% at week 8 compared with baseline. There was a significant effect of diet on plasma HDL-cholesterol concentrations (P < 0.005 by one-way ANOVA with repeated measures). However, a group difference was observed only between baseline and week 12 (16% increase; P < 0.05 by Bonferroni correction). Triacylglycerol concentrations did not change. CONCLUSIONS: The yeast-derived beta-glucan fiber significantly lowered total cholesterol concentrations and was well tolerated; HDL-cholesterol concentrations rose, but only 4 wk after the fiber was stopped.
PMID: 10426696 [PubMed - indexed for MEDLINE]
3
A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial.
Gordon M, Bihari B, Goosby E, Gorter R, Greco M, Guralnik M, Mimura T, Rudinicki V, Wong R, Kaneko Y.
AIDS Activities Division, San Francisco General Hospital, CA, USA.
Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).
Publication Types:
PMID: 10503166 [PubMed - indexed for MEDLINE]
4
PGG-glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)-glucan receptor.
Wakshull E, Brunke-Reese D, Lindermuth J, Fisette L, Nathans RS, Crowley JJ, Tufts JC, Zimmerman J, Mackin W, Adams DS.
Department of Biology, Alpha-Beta Technology, Worcester, MA 01605, USA. ewaksh@abti.com
PGG-Glucan, a soluble beta-(1,6)-branched beta-(1,3)-linked glucose homopolymer derived from the cell wall of the yeast Saccharomyces cerevisiae, is an immunomodulator which enhances leukocyte anti-infective activity and enhances myeloid and megakaryocyte progenitor proliferation. Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of subsequently isolated blood leukocytes to both soluble and particulate activators in a dose-dependent manner, and increased leukocyte microbicidal activity. No evidence for inflammatory cytokine production was obtained under these conditions. Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an NF-kappaB-like nuclear transcription factor in purified human neutrophils. The binding of 3H-PGG-Glucan to human leukocyte membranes was specific, concentration-dependent, saturable, and high affinity (Kd approximately 6 nM). A monoclonal antibody specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the NF-kappaB-like factor by PGG-Glucan, and ligand binding data, including polysaccharide specificity, suggested that the PGG-Glucan binding moiety was lactosylceramide. These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and human neutrophils is mediated by the glycosphingolipid lactosylceramide present at the cell surface.
PMID: 10102791 [PubMed - indexed for MEDLINE]
5
The effect of (1-->3)-beta-D-glucans, carboxymethylglucan and schizophyllan on human leukocytes in vitro.
Kubala L, Ruzickova J, Nickova K, Sandula J, Ciz M, Lojek A.
Institute of Biophysics Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
(1-->3)-beta-D-glucans are known as potent inductors of humoral and cell-mediated immunity in humans and animals. (1-->3)-beta-D-glucans isolated from various sources differ in their chemical structure and physical parameters and consequently in their immunomodulatory potential. In this study the immunomodulatory activity of two (1-->3)-beta-D-glucans schizophyllan (SPG) and carboxymethylglucan (CMG) was determined and compared on human blood leukocytes in vitro. Both SPG and CMG activated blood phagocytes and lymphocytes as demonstrated by increased whole blood production of reactive oxygen species, by increased production of pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha, by increased surface expression of CD69 on lymphocytes, and by altered expression of CD11b and CD62L on polymorphonuclear leukocytes and monocytes. SPG demonstrated a significantly higher potential to stimulate blood phagocytes and production of selected pro-inflammatory cytokines than CMG. The higher potency of SPG to stimulate human blood phagocytes in vitro could be caused by factors such as higher branching frequencies or neutral polymer charge of SPG or different conformation in solution if compared with CMG.
PMID: 14667704 [PubMed - in process]
6
Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells.
Hong F, Hansen RD, Yan J, Allendorf DJ, Baran JT, Ostroff GR, Ross GD.
James Graham Brown Cancer Center and. Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
The tumor-killing mechanisms available to monoclonal antibodies (mAbs; e.g., antagonism of growth factor receptors, antibody-dependent cell-mediated cytotoxicity) limit efficacy. Previous studies suggested that i.v. beta-glucan might function as an adjuvant for antitumor mAbs. beta- Glucan had been shown to function via the iC3b-receptor complement receptor 3 (CR3; CD11b/CD18) thereby enhancing leukocyte killing of tumor cells coated with iC3b via naturally occurring antitumor antibodies. Therapy with beta-glucans was limited by levels of natural antibodies and by tumor escape through elimination of antigen-positive cells. Accordingly, it was hypothesized that beta-glucan responses could be improved by combined administration with antitumor mAbs. Five tumor models were explored in BALB/c or C57Bl/6 mice using tumors that expressed either high levels of naturally occurring antigens (e.g., G(D2) ganglioside) or recombinant human MUC1. In comparison with antitumor mAb or beta-glucan alone, combined treatment with mAb plus beta-glucan produced significantly greater tumor regression in all models that included mammary, s.c., and hepatic tumors. Tumor-free survival only occurred in models that incorporated stable expression of the target antigen. beta-Glucan enhancement of the mAb tumoricidal response did not occur in mice deficient in either leukocyte CR3 (CD11b(-/-)) or serum C3, confirming the requirement for CR3 on leukocytes and iC3b on tumors. Granulocytes appeared to be primarily responsible for tumoricidal activity, because beta-glucan therapeutic responses did not occur in granulocyte-depleted mice. These data suggest that the therapeutic efficacy of mAbs known to activate complement (e.g., Herceptin, Rituxan, and Erbitux) could be significantly enhanced if they were combined with beta-glucan.
PMID: 14695221 [PubMed - in process]
7
Protection against experimental intraabdominal sepsis by two polysaccharide immunomodulators.
Tzianabos AD, Gibson FC 3rd, Cisneros RL, Kasper DL.
J Infect Dis. 1998 Jul;178(1 ):200-6.
Two immunomodulating polysaccharides, poly-(1-6)-beta-glucotriosyl-(1-3)-beta- glucopyranose (PGG)-glucan and Bacteroides fragilis polysaccharide A (PS A), were evaluated for the prevention of mortality and abscess formation associated with experimental intraabdominal sepsis. Prophylactic treatment with a combination of these compounds significantly reduced mortality (8% vs. 44% in the saline-treated control group) and the incidence of abscesses (30% vs. 100% in the saline-treated control group) after challenge with rat cecal contents. These compounds were also effective when administered therapeutically after bacterial contamination of the peritoneal cavity. PS A treatment conferred long-term protection against abscess formation and resulted in significantly fewer total aerobes and anaerobes in the peritoneal fluid of animals challenged with cecal contents. These data demonstrate the usefulness of two immunomodulatory polysaccharides in preventing experimental intraabdominal sepsis in the absence of antimicrobial therapy and may represent a new adjunct to antibiotic regimens currently used to prevent clinical cases of this disease.
PMID: 9652441 [PubMed -indexed for MEDlINE]
8
Synergism between poly-(1-6)-beta-D- glucopyranosyl-(1-3)-beta-D- glucopyranose glucan and cefazolin in prophylaxis of staphylococcal wound infection in a guinea pig model.
Kaiser AB, Kernodle OS.
Antimicrob Agents Chemother. 1998 Sep;42(9):2449-51.
To determine whether the infection-preventing capability of the neutrophil-activating agent poly-( 1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan (PGG- glucan) can be enhanced with antibiotic prophylaxis, we administered PGG-glucan and cefazolin, alone and in combination, to guinea pigs inoculated with isolates of staphylococci. Guinea pigs receiving both PGG-glucan and cefazolin had 50% infective doses that were 8- to 20-fold higher than those obtained with cefazolin alone and 100- to 200-fold higher than those obtained with PGG-glucan alone. PGG-glucan and cefazolin are synergistic in their ability to prevent staphylococcal wound infection.
PMID: 9736583 [PubMed -indexed for MEDLlNE]
9
A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients.
Babineau T J, Hackford A, Kenler A, Bistrian B, Forse RA, Fairchild PG, Heard S, Keroack M, Caushaj P, Benotti P.
Arch Surg. 1994 Nov;129(11):1204-10.
OBJECTIVE: To examine the safety and efficacy of multiple doses of PGG-glucan )(poly-[1-6]-B-D-glucopyranosyl-[1-3]-B-D-glucopyranose in high-risk patients undergoing major thoracic or abdominal surgery. DESIGN: An interventional, multicenter, double-blind, randomized, placebo-controlled study. SETTING: Four university-affiliated medical centers. PATIENTS: Sixty-seven high-risk patients undergoing major thoracic or abdominal surgery. INTERVENTION: Patients were randomized in a 1:1:1:1 ratio to receive saline placebo or PGG-glucan at a dose of 0.1 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or 2.0 mg/kg. One dose was administered before surgery and three doses were administered after surgery. MAIN OUTCOME MEASURES: To examine the safety and efficacy of PGG-glucan infusion and to identify potentially important factors for a planned phase III study. RESULTS: A dose- response trend with regard to infection incidence among patients who received PGG- glucan was observed. Serious infections occurred in four patients who received placebo and in three patients who received PGG-glucan at a dose of 0.1 mg/kg. However, only one patient who received PGG-glucan at a high dose had a serious infection. The incidence and severity of adverse events was comparable in all groups. CONCLUSIONS: PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation in a planned phase III trial.
PMID: 7979954 [PubMed -indexed for MEDLlNE]
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