β-Glucans are polysaccharide

Polysaccharide

Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...

s 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

Cellulose

Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....

 in plants, the bran

Bran

Bran is the hard outer layer of grain and consists of combined aleurone and pericarp. Along with germ, it is an integral part of whole grains, and is often produced as a by-product of milling in the production of refined grains. When bran is removed from grains, the grains lose a portion of their...

 of cereal grains, the cell wall of baker's yeast

Baker's yeast

Baker's yeast is the common name for the strains of yeast commonly used as a leavening agent in baking bread and bakery products, where it converts the fermentable sugars present in the dough into carbon dioxide and ethanol...

, certain fungi

Fungus

A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

, mushroom

Mushroom

A mushroom is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or on its food source. The standard for the name "mushroom" is the cultivated white button mushroom, Agaricus bisporus; hence the word "mushroom" is most often applied to those fungi that...

s and bacteria. Some forms of beta glucans are useful in human nutrition

Human nutrition

Human nutrition is the provision to humans to obtain the materials necessary to support life. In general, humans can survive for two to eight weeks without food, depending on stored body fat and muscle mass. Survival without water is usually limited to three or four days...

 as texturing agents and as soluble fiber supplements, but can be problematic in the process of brewing

Brewing

Brewing is the production of beer through steeping a starch source in water and then fermenting with yeast. Brewing has taken place since around the 6th millennium BCE, and archeological evidence suggests that this technique was used in ancient Egypt...

.

Yeast and medicinal mushroom derived β-glucans are notable for their ability to modulate the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

. Research has shown that insoluble (1,3/1,6) β-glucan, has greater biological activity

Biological activity

In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or pharmacophore but can be modified by the other...

 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.

Overview

β-Glucans are polysaccharides that contain only glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 as structural components, and are linked with β-glycosidic bonds.

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

Aldose

An aldose is a monosaccharide that contains only one aldehyde group per molecule. The chemical formula takes the form Cnn. The simplest possible aldose is the diose glycolaldehyde, which only contains two carbon atoms....

 monosaccharide (or the number 2 carbon of a ketose

Ketose

A ketose is a sugar containing one ketone group per molecule.With 3 carbon atoms, dihydroxyacetone is the simplest of all ketoses and is the only one having no optical activity. Ketoses can isomerize into an aldose when the carbonyl group is located at the end of the molecule...

 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

Haworth projection

A Haworth projection is a common way of representing the cyclic structure of monosaccharides with a simple three-dimensional perspective.The Haworth projection was named after the English chemist Sir Norman Haworth....

). 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.

Beta-glucan chemistry

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

Polysaccharide-K

Polysaccharide-K is a protein-bound polysaccharide, which is used as an immune system boosting agent in the treatment of cancer in some countries in Europe as well as China and Japan. In Japan, PSK is approved as an adjuvant for cancer therapy and is covered by government health insurance...

.

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

Saccharomyces cerevisiae

Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

). However, β(1,3)(1,4)-glucans are also extracted from the bran of some grains such as oats

OATS

OATS - Open Source Assistive Technology Software - is a source code repository or "forge" for assistive technology software. It was launched in 2006 with the goal to provide a one-stop “shop” for end users, clinicians and open-source developers to promote and develop open source assistive...

 and barley

Barley

Barley is a major cereal grain, a member of the grass family. It serves as a major animal fodder, as a base malt for beer and certain distilled beverages, and as a component of various health foods...

, and to a much lesser degree in rye

Rye

Rye is a grass grown extensively as a grain and as a forage crop. It is a member of the wheat tribe and is closely related to barley and wheat. Rye grain is used for flour, rye bread, rye beer, some whiskeys, some vodkas, and animal fodder...

 and wheat

Wheat

Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...

. 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

Shiitake

The Shiitake is an edible mushroom native to East Asia, which is cultivated and consumed in many Asian countries, as well as being dried and exported to many countries around the world. It is a feature of many Asian cuisines including Vietnamese, Chinese, Japanese, Korean and Thai...

, 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 at the University of Louisville discovered that a receptor on the surface of innate immune cells called Complement Receptor 3

Macrophage-1 antigen

Macrophage-1 antigen is a complement receptor consisting of CD11b and CD18.It binds to C3b and C4b.-Function:...

 (CR3

Macrophage-1 antigen

Macrophage-1 antigen is a complement receptor consisting of CD11b and CD18.It binds to C3b and C4b.-Function:...

 or CD11b/CD18

CD18

Integrin beta-2 is a protein that in humans is encoded by the ITGB2 gene.It is the beta subunit of four different structures:* LFA-1 * Macrophage-1 antigen * Integrin alphaXbeta2...

) is responsible for binding to beta-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.

Research

Tumoricidal effects

The tumoricidal properties of beta-glucans have been studied in several in vitro and in vivo animal models. In a mouse model study, beta 1,3 glucan in conjunction with interferon gamma inhibited tumors and liver metastasis. In some studies, beta-1,3 glucans enhanced the effects of chemotherapy. In a mouse carcinoma model, beta-1,3 glucans did not reduce tumor incidence but was associated with reduced mortality in combination with cyclophosphamide

Cyclophosphamide

Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

. In human patients with advanced gastric or colorectal cancer, the administration of beta-1,3 glucans derived from shiitake

Shiitake

The Shiitake is an edible mushroom native to East Asia, which is cultivated and consumed in many Asian countries, as well as being dried and exported to many countries around the world. It is a feature of many Asian cuisines including Vietnamese, Chinese, Japanese, Korean and Thai...

 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 that received the PGG-glucan

PGG-glucan

"poly-[1-6]--D-glucopyranosyl-[1-3]--D-glucopyranose glucan "Proprietary name Betafectin- What is it :"Betafectin PGG-Glucan, a novel β- branched β- glucan purified from the cell walls of Saccharomyces cerevisiae"...

 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 that there was decreased use of intravenous antibiotics and shorter stays in the intensive care unit 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 4 patients that received the placebo, 3 patients that received the low dose (0.1 mg/kg) of PGG-Glucan. and 1 patient that received the highest dose of 2.0 mg/kg of PGG-Glucan.

The results of a phase III human clinical trial showed that PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations. This study was conducted in patients that were already as high-risk because of the type of surgery and were more susceptible to infections and other complications.

A phase III clinical trial was proposed and conducted at thirty-nine medical centers in the U.S. involving 1,249 subjects stratified according to colorectal or non-colorectal surgical patients. The PGG-glucan was given once pre-operatively and three times post-operative at 0, 0.5 or 1.0 mg/kg body weight. The measured outcome was serious infection or death of the subjects within 30 days post-surgery. Injectable PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations.

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. 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 post-exposure test period. Mice treated with 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.

Radiation exposure

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 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 i.v. β-glucan. Other reports showed that β-glucan could reverse the myelo-suppression 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 that β-glucan could enhance granulocyte and megakaryocyte colony formation by hematopoietic stem progenitor cells when used in combination with GM-CSF and interleukin-3 (IL-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. A study by Allendorf et al. clearly demonstrated that oral Beta glucan had hematopoietic effects analogous to Beta glucan administered by i.v. methods, work of Vetvicka’s group showed the mechanisms of the glucan transfer through the gastrointestinal tract. Allendorf et al. demonstrated that orally administered whole glucan particulate functions to accelerate hematopoiesis following irradiation in an analogous manner as i.v. administered β-glucan. Experiments by Cramer et al. or Vetvicka clearly demonstrated that oral β-glucan stimulates hematopoiesis in radiation-treated mice.

Septic shock

Early research by Onderdonk et al. investigated the ability of yeast b-glucan to reduce septic infections using in vivo models. Onderdonk et al. 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 hours prior to infection. Work by Kernodle et al. demonstrated that 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.

Surgery

In a prospective, randomized, double-blind study, 38 trauma patients received an I.V. of a soluble yeast derived glucan for 7 days or placebo. The total mortality rate was significantly less in the glucan group (0% vs. 29%). There was 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 C. albicans and midline laparotomy

Laparotomy

A laparotomy is a surgical procedure involving a large incision through the abdominal wall to gain access into the abdominal cavity. It is also known as coeliotomy.- Terminology :...

. The non-operated mice on glucan had a 100% survival vs. 73% in the surgical group.

Allergic rhinitis

This disease is caused by an IgE

IGE

IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...

-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.

Arthritis

Using paramagnetic resonance spectroscopy, yeast-derived glucan was found to cause decline in oxidative tissue damage during the progress of arthritic diseases, suggesting the role in treatment of arthritis.

Additional applications

Influence of certain cereals (barley, oats) and edible mushrooms upon decrease of levels of serum cholesterol and liver low-density lipoproteins, leading to lowering of atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

 and cardiovascular disease

Cardiovascular disease

Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

 hazards, is also mediated by β-glucans. It is known that cereals, mushrooms and yeast facilitate bowel motility and can be used in amelioration of intestinal problems, particularly obstipation. Non-digestible b-glucans, forming a remarkable portion of these materials, are also able to modulate mucosal immunity of the intestinal tract.

β-glucan absorption

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 beta 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

Gut-associated lymphoid tissue

The digestive tract's immune system is often referred to as gut-associated lymphoid tissue and works to protect the body from invasion. GALT is an example of mucosa-associated lymphoid tissue.-Function:...

.

β-D-glucan's role in diagnostics

β-D-glucan (properly known as (1→3)β-D-glucan, but also incorrectly called 1,3-β-D-glucan or even just glucan) forms part of the cell wall of certain medically important fungi, especially Aspergillus

Aspergillus

Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli...

and Agaricus

Agaricus

Agaricus is a large and important genus of mushrooms containing both edible and poisonous species, with possibly over 300 members worldwide...

species. An assay to detect the presence of (1→3)β-D-glucan in the blood has been produced by Associates of Cape Cod called Fungitell and is marketed as a means of diagnosing invasive fungal infection in patients.

False positives may occur because of fungal contaminants in the antibiotic, amoxicillin-clavulanate. Streptococcus pneumoniae

Streptococcus pneumoniae

Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...

, Pseudomonas aeruginosa

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...

 and Alcaligenes faecalis

Alcaligenes faecalis

Alcaligenes faecalis is a Gram-negative, rod-shaped, motile, non-nitrate reducing, oxidase positive, catalase positive, beta hemolytic, and citrate positive obligate aerobe that is commonly found in the environment. It was originally named for its first discovery in feces, but was later found to be...

also produce (1→3)β-D-glucan.

Literature

• ARTHUR O. TZIANABOS Polysaccharide Immunomodulators as Therapeutic Agents, Harvard Medical School, Boston, USA - 2000