β-Glucans (beta-glucans) are polysaccharides of D-glucose monomers linked by β-glycosidic bonds. β-glucans are a diverse group of molecules that can vary with respect to molecular mass, solubility, viscosity, and three-dimensional configuration. They occur most commonly as cellulose in plants, the bran of cereal grains, the cell wall of baker's yeast, certain fungi, mushrooms and bacteria. Some forms of beta glucans are useful in human nutrition as texturing agents and as soluble fiber supplements, but can be problematic in the process of brewing.
Oat is a rich source of the water-soluble fibre (1,3/1,4) β-glucan, and its effects on health have been extensively studied the last 30 years. Oat β-glucans are the only dietary fiber being recognized by the European Food Safety Authority (EFSA) to be able to reduce a disease risk. Oat β-glucans can be highly concentrated in different types of oat brans.
Yeast and medicinal mushroom derived β-glucans are notable for their ability to modulate the immune system. One study has shown that insoluble (1,3/1,6) β-glucan, has greater biological activity than that of its soluble (1,3/1,4) β-glucan counterparts. The differences between β-glucan linkages and chemical structure are significant in regards to solubility, mode of action, and overall biological activity.
Glycosidic bonds are etheric oxygen bridges which link the monosaccharide units in a polysaccharide, and they are designated by a pair of numbers to indicate which carbons in each of the monosaccharide units are linked (according to the standard numbering for simple monosaccharides). When a glycosidic bond involves the number 1 carbon of an aldose monosaccharide (or the number 2 carbon of a ketose monosaccharide), a second designation is needed to indicate the spatial orientation of the etheric oxygen linkage at that carbon (the anomeric carbon). An "α-" (alpha) indicates the etheric oxygen linkage attaches to the anomeric carbon below the ring, and a "β-" (beta) indicates the etheric oxygen linkage attaches to the anomeric carbon above the ring (in the standard Haworth projection). The orientation of the etheric linkage at any of the other carbons is predetermined and fixed by the identity of the monosaccharide and the position, and no further descriptor is required for the glycosidic bond.
Thus, the designation of β(1-3) for a glycosidic linkage indicates that the etheric oxygen bridge between two consecutive monosaccharide units of the polysaccharide connects the number 1 carbon of the first unit to the number 3 carbon of the second unit, and that etheric oxygen bridge attaches to carbon 1 of the first unit from above the ring.
Likewise, the designation of β(1-6) for a glycosidic linkage indicates that the etheric oxygen bridge between two consecutive monosaccharide units of the polysaccharide connects the number 1 carbon of the first unit to the number 6 carbon of the second unit, and that etheric oxygen bridge attaches to carbon 1 of the first unit from above the ring.
By definition, beta-glucans are chains of D-glucose polysaccharides, linked by beta type glycosidic bonds. These six-sided D-glucose rings can be connected to one another, on a variety of positions on the D-glucose ring structure. Some β-glucan compounds are continual repeats of D-glucose attached at a specific position.
However, β-glucans can be more diverse than molecules like starch. For instance, a β-glucan molecule can be composed of repeating D-glucose units linked with β-glycosidic bonds at one position like starch, but have branching glucose side-chains attached to other positions on the main D-glucose chain. These smaller side-chains can branch off the β-glucan “backbone" (in the case of starch, the backbone would be D-glucose chains linked at the (1,4) position) at other positions like that of the 3 and 6 position. In addition, these side-chains can be attached to other types of molecules, like proteins. An example of a β-glucan that has proteins attached to it is Polysaccharide-K.
The most active forms of β-glucans are those comprising D-glucose units with (1,3) links and with side-chains of D-glucose attached at the (1,6) position. These are referred to as β-1,3/1,6 glucan. Some researchers have suggested that it is the frequency, location, and length of the side-chains rather than the backbone of β-glucans that determine their immune system activity. Another variable is the fact that some of these compounds exist as single strand chains, while the backbones of other β(1,3)-glucans exist as double or triple stranded helix chains. In some cases, proteins linked to the β(1,3)-glucan backbone may also be involved in providing therapeutic activity. Although these compounds can potentially enhance immune function, it must be emphasized that this research is in its infancy. In addition, there are differing opinions on which molecular weight, shape, structure, and source of β(1,3)-glucans provide the greatest biological activity.
β-glucan sources in nature
One of the most common sources of β(1,3)D-glucan for supplement use is derived from the cell wall of baker’s yeast (Saccharomyces cerevisiae). However, β(1,3)(1,4)-glucans are also extracted from the bran of some grains, such as oats and barley, and to a much lesser degree in rye and wheat. The β(1,3)D-glucans from yeast are often insoluble. Those extracted from grains tend to be both soluble and insoluble. Other sources include some types of seaweed, and various species of mushrooms, such as reishi, shiitake, and maitake.
β-Glucan and the immune system
β-Glucans are known as "biological response modifiers" because of their ability to activate the immune system. Immunologists have discovered that receptors on the surface of innate immune cells called dectin-1 and complement receptor 3 (CR3 or CD11b/CD18) are responsible for binding to β-glucans, allowing the immune cells to recognize them as "non-self". 
β-glucan and blood cholesterol
Several health claims requests were submitted to the EFSA NDA Panel (Dietetic Products, Nutrition and Allergies), related to the role of β-glucans in "maintenance of normal blood cholesterol concentrations and maintenance or achievement of a normal body weight". In July 2009, the Scientific Committee issued the following statements:
- On the basis of the data available, the Panel concludes that a cause and effect relationship has been established between the consumption of beta-glucans and the reduction of blood cholesterol concentrations.
- The following wording reflects the scientific evidence: "Regular consumption of beta-glucans contributes to maintenance of normal blood cholesterol concentrations". In order to bear the claim, foods should provide at least 3 g/d of beta-glucans from oats, oat bran, barley, barley bran, or from mixtures of non-processed or minimally processed beta-glucans in one or more servings. The target population is adults with normal or mildly elevated blood cholesterol concentrations.
- On the basis of the data available the Panel concludes that a cause and effect relationship has not been established between the consumption of beta-glucans and the maintenance or achievement of a normal body weight.
In November 2011, the EU Commission published its decision in favour of oat beta-glucans in respect of Article 14 of the EC Regulation on the labelling of foodstuffs with nutrition and health claim statements permitting oat beta-glucan to be described as beneficial to health. Following the opinion of the Panel on Dietetic Products, Nutrition and Allergies (NDA) the EFSA and the Regulation (EU) no. 1160/2011 of the Commission, foodstuffs through which 3g/day of oat beta-glucan are consumed (1g of oat beta-glucan per portion) are allowed to display the following health claim: «Oat beta-glucan reduces the cholesterol level in the blood. The lowering of the blood cholesterol level can reduce the risk of coronary heart disease.»
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The tumoricidal properties of β-glucans have been studied in several in vitro and in vivo animal models. In a mouse model study, β-1,3 glucan in conjunction with interferon gamma inhibited tumors and liver metastasis. In some studies, β-1,3 glucans enhanced the effects of chemotherapy. In a mouse carcinoma model, β-1,3 glucans did not reduce tumor incidence, but were associated with reduced mortality in combination with cyclophosphamide. In human patients with advanced gastric or colorectal cancer, the administration of β-1,3 glucans derived from shiitake mushrooms, in conjunction with chemotherapy, resulted in prolonged survival times.
Prevention of infection
Alpha-Beta Technologies conducted a series of human clinical trials in the 1990s to evaluate the impact of β-glucan therapy for controlling infections in high-risk surgical patients. In the initial trial, 34 patients were randomly (double-blind, placebo-controlled) assigned to treatment or placebo groups. Patients who received the PGG-glucan had significantly fewer infectious complications than the placebo group (1.4 infections per infected patient for PGG-glucan group vs. 3.4 infections per infected patient for the placebo group). Additional data from the clinical trial revealed intravenous antibiotic use was decreased, and stays in the intensive care unit were shorter for the patients receiving PGG-glucan vs. patients receiving the placebo.
A subsequent human clinical trial studied the effect of β-glucan on the incidence of infection in high-risk surgical patients. A total of 67 patients were randomized to treatment with a placebo or a dose of 0.1, 0.5, 1.0 or 2.0 mg PGG-glucan per kilogram of body weight. Serious infections occurred in four patients who received the placebo, three patients who received the low dose (0.1 mg/kg) of PGG-glucan, and one patient who received the highest dose of 2.0 mg/kg.
The results of a phase III human clinical trial showed that PGG-glucan therapy reduced serious postoperative infections by 39% after high-risk noncolorectal operations. This study was conducted in patients who were already at high risk because of the type of surgery and were more susceptible to infections and other complications.
A study conducted by the Canadian Department of Defense showed that orally administered yeast β-glucan given with or without antibiotics protected mice against anthrax infection.[dead link][unreliable source?] A dose of antibiotics along with oral whole glucan particles (2 mg/kg body weight or 20 mg/kg body weight) for eight days prior to infection with Bacillus anthracis protected mice against anthrax infection over the 10-day postexposure test period. Mice treated with the antibiotic alone did not survive.
A second experiment was conducted to investigate the effect of yeast β-glucan orally consumed after exposure of mice to B. anthracis. The results were similar to the previous experiment, with an 80-90% survival rate for mice treated with β-glucan, but only 30% for the control group after 10 days of exposure.
Early research by Onderdonk et al. investigated the ability of yeast b-glucan to reduce septic infections using in vivo models. They found that mice challenged with E. coli or S. aureus bacteria were protected against septic infections when they were injected with PGG-glucan 4–6 hr prior to infection. Preventative dosing of yeast β-glucan prior to infection with S. aureus prevented sepsis in a guinea pig model. Research has been conducted in animals on the use of yeast β-glucans for the treatment and prophylaxis of bacterial sepsis and protection against oxidative organ injury.
In a prospective, randomized, double-blind study, 38 trauma patients received a soluble, yeast-derived glucan intravenously for seven days or placebo. The total mortality rate was significantly less in the glucan group (0% vs. 29%), with also a decrease in septic morbidity (9.5% vs. 49%).
Yeast-derived beta-glucan significantly enhanced phagocytic activity in an experimental mouse model of sepsis induced by Candida albicans and midline laparotomy. Mice not operated on, on glucan, had a 100% survival vs. 73% in the surgical group.
Specific hematopoietic activity was first demonstrated with β-glucan in the mid-1980s in an analogous manner as granulocyte monocyte–colony stimulating factor (GM-CSF). Research was carried out initially with particulate β-glucan and later with soluble β-glucans, all of which were administered intravenously (IV) to mice. Mice exposed to 500-900 cGy (500-900 mrads) of gamma radiation exhibited a significantly enhanced recovery of blood leukocyte, platelet and red blood cell counts when given IV β-glucan. Other reports showed that β-glucan could reverse the myelosuppression produced with chemotherapeutic drugs such as fluorouracil, carboplatinum, or cyclophosphamide. Moreover, the anti-infective activity of β-glucan combined with its hematopoiesis-stimulating activity resulted in enhanced survival of mice receiving a lethal dose of 900-1200 cGy of radiation. In vitro studies showed β-glucan could enhance granulocyte and megakaryocyte colony formation by hematopoietic stem progenitor cells when used in combination with GM-CSF and interleukin-3, respectively.
Original studies delivered glucan almost entirely by injection. Later, numerous studies tried to evaluate the possibility that glucan can be delivered orally without compromising its biological activities, opening the oral route of administration as a more pleasant alternative. Oral beta-glucan had hematopoietic effects analogous to beta-glucan administered by IV, and orally administered whole glucan particulate functions to accelerate hematopoiesis following irradiation in an analogous manner as IV-administered β-glucan. The mechanisms of the glucan transfer through the gastrointestinal tract were reported. Oral β-glucan stimulates hematopoiesis in radiation-treated mice.
This disease is caused by an IgE-mediated allergic inflammation of the nasal mucosa. Orally administered yeast-glucan decreased levels of IL-4 and IL-5 cytokines responsible for the clinical manifestation of this disease, while increased the levels of IL-12.
A study employing paramagnetic resonance spectroscopy indicated that yeast-derived beta-glucan could reduce free-radical formation in vitro and reduce the plasma levels of protein carbonyls in a rodent arthritis model.
Consuming certain cereals (barley, oats) and edible mushrooms decreases the levels of serum cholesterol and liver low-density lipoproteins, leading to lowering of atherosclerosis and cardiovascular disease hazards; this is also mediated by β-glucans. These cereals, mushrooms, and yeast facilitate bowel motility and can be used in amelioration of intestinal problems, particularly obstipation. Indigestible β-glucans, forming a remarkable portion of these materials, are also able to modulate mucosal immunity of the intestinal tract.
For maximal absorption, oral β(1,3)-D-glucan should be taken on an empty stomach. Enterocytes reportedly facilitate the transportation of β(1,3)-glucans and similar compounds across the intestinal cell wall into the lymph, where they begin to interact with macrophages to activate immune function. Radiolabeled studies have verified that both small and large fragments of β-glucans are found in the serum, which indicates they are absorbed from the intestinal tract. M cells within the Peyer’s patches physically transport the insoluble whole glucan particles into the gut-associated lymphoid tissue.
Role in diagnostics
β-D-Glucan forms part of the cell wall of certain medically important fungi, especially Aspergillus and Agaricus species. An assay to detect its presence in blood is marketed as a means of diagnosing invasive fungal infection in patients.
False positives may occur because of fungal contaminants in the antibiotics amoxicillin-clavulanate, and piperacillin/tazobactam. False positives can also occur with contamination of clinical specimens with the bacteria Streptococcus pneumoniae, Pseudomonas aeruginosa, and Alcaligenes faecalis which also produce (1→3)β-D-glucan.
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