Jump to content

Beta-glucan: Difference between revisions

From Wikipedia, the free encyclopedia
Content deleted Content added
m clean up, Replaced: 4-6 hours → 4–6 hours using AWB
Ksero (talk | contribs)
Convert to proper inline references and some cleanup
Line 1: Line 1:
{{Cleanup|date=September 2007}}
{{Cleanup|date=September 2007}}


'''β-Glucans''' (or '''beta-[[glucans]]''') are [[polysaccharide]]s occurring in the [[bran]] of [[cereal grain]]s, the cell wall of baker's yeast, certain types of fungi, and many kinds of mushrooms. The cereal based beta glucans occur most abundantly in [[barley]] and [[oat]]s and to a much lesser degree in [[rye]] and [[wheat]]. They are useful in [[human nutrition]] as [[texturing agent]]s and as [[soluble fiber]] supplements, but problematic in [[brewing]] as excessive levels make the [[wort]] too viscous. An insoluble (1,3/1,6) beta glucan derived from baker's yeast has a different molecular structure than that of its soluble (1,3/1,4) counterparts and has a greater biological activity due to its structural "branching". Yeast derived beta glucans are notable for their immunomodulatory function. The differences between soluble and insoluble beta glucans are significant in regards to application, mode of action, and overall biological activity.
'''β-Glucans''' (or '''beta-[[glucans]]''') are [[polysaccharide]]s occurring in the [[bran]] of [[cereal grain]]s, the cell wall of baker's yeast, certain types of [[fungus|fungi]], and many kinds of [[mushroom]]s. The cereal based beta-glucans occur most abundantly in [[barley]] and [[oat]]s and to a much lesser degree in [[rye]] and [[wheat]]. They are useful in [[human nutrition]] as [[texturing agent]]s and as [[soluble fiber]] supplements, but problematic in [[brewing]] as excessive levels make the [[wort]] too viscous. An insoluble (1,3/1,6) beta glucan derived from baker's yeast has a different molecular structure than that of its soluble (1,3/1,4) counterparts and has a greater biological activity due to its structural "branching". Yeast derived beta glucans are notable for their immunomodulatory function. The differences between soluble and insoluble beta glucans are significant in regards to application, mode of action, and overall biological activity.


== Overview==
== Overview==
[[Glucans]] are polysaccharides that only contain [[glucose]] as structural components. Beta 1, 3-D glucans are chains of D-glucose molecules, with the six-sided D-glucose rings connected at the 1 and 3 positions. Smaller side chains branch off the 1,3 polysaccharide “backbone.” The most active form of Beta 1, 3-D glucans are apparently those that contain 1,6 side-chains branching off from the longer beta-1,3 glucan backbone. These are referred to as beta-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 beta 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 beta-1,3 glucans exist as double or triple stranded helix chains. In some cases, proteins linked to the beta-1,3 glucan backbone may also be involved in providing therapeutic activity. Although these compounds have exciting potential for enhancement of the immune system, it must be emphasized that this research is in its infancy, and there are differing opinions on which molecular weight, shape, structure, and source of beta-1, 3 glucans provide the greatest therapeutic benefit.
[[Glucans]] are polysaccharides that only contain [[glucose]] as structural components. Beta 1,3-D glucans are chains of D-glucose molecules, with the six-sided D-glucose rings connected at the 1 and 3 positions. Smaller side chains branch off the 1,3 polysaccharide “backbone.” The most active form of Beta 1,3-D glucans are apparently those that contain 1,6 side-chains branching off from the longer beta-1,3 glucan backbone. These are referred to as beta-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 beta 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 beta-1,3 glucans exist as double or triple stranded helix chains. In some cases, proteins linked to the beta-1,3 glucan backbone may also be involved in providing therapeutic activity. Although these compounds have exciting potential for enhancement of the immune system, it must be emphasized that this research is in its infancy, and there are differing opinions on which molecular weight, shape, structure, and source of beta-1,3 glucans provide the greatest therapeutic benefit.


One of the most common sources of Beta 1, 3-D glucan is derived from the cell wall of baker’s yeast (Saccharomyces cerevisiae). However, beta-1,3 glucans are also extracted from the bran of some grains such as oats and barley. The Beta 1, 3-D glucans from yeast are often insoluble whereas those extracted from grains tend to be soluble. Other sources include some types of seaweed [1], and various species of mushrooms such as [[Reishi]], [[Shiitake]], and [[Maitake]].[2]
One of the most common sources of Beta 1,3-D glucan is derived from the cell wall of baker’s yeast (Saccharomyces cerevisiae). However, beta-1,3 glucans are also extracted from the bran of some grains such as oats and barley. The Beta 1,3-D glucans from yeast are often insoluble whereas those extracted from grains tend to be soluble. Other sources include some types of seaweed,<ref>{{cite journal | last = Teas | first = J | year = 1983 | title = The dietary intake of Laminarin, a brown seaweed, and breast cancer prevention | journal = Nutrition and cancer | volume = 4 | issue = 3 | pages = 217-222 | publisher = [[Lawrence Erlbaum Associates]] | issn = 0163-5581 | pmid = 6302638 }}</ref> and various species of mushrooms such as [[Reishi]], [[Shiitake]], and [[Maitake]].<ref>{{cite journal | last = Wasser | first = SP | coauthors = Weis AL | year = 1999 | title = Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective | journal = Critical reviews in immunology | volume = 19 | issue = 1 | pages = 65-96 | publisher = Begell House | location = United States | issn = 1040-8401 | pmid = 9987601 }}</ref>


Beta 1, 3-D glucans are being referred to as biological response modifiers because of their ability to activate the immune system.[3] However, it should be noted that the activity of Beta 1, 3-D glucan is different from agents that stimulate the immune system. Agents that stimulate the immune system can push the system to over-stimulation, and hence are contraindicated in individuals with autoimmune diseases, allergies, or yeast infections. Beta 1, 3-D glucans seem to make the immune system work better without becoming overactive. They accomplish this by activating [[phagocytes]], which are immune system cells whose function is to trap and destroy foreign substances in our bodies such as bacteria, viruses, fungi, and parasites.[4] In addition to enhancing the activity of phagocytes, beta-1,3 glucans also reportedly lower elevated levels of LDL cholesterol, aid in wound healing, help prevent infections, enhance NK cell function, and help in the prevention and treatment of cancer.
Beta 1,3-D glucans are being referred to as biological response modifiers because of their ability to activate the immune system.<ref>{{cite journal | last = Miura | first = NN | coauthors = Ohno N, Aketagawa J, Tamura H, Tanaka S, Yadomae T | date = | year = 1996 | month = January | title = Blood clearance of (1-->3)-beta-D-glucan in MRL lpr/lpr mice | journal = FEMS immunology and medical microbiology | volume = 13 | issue = 1 | pages = 51-57 | publisher = [[Blackwell Publishing]] | location = England | issn = 0928-8244 | pmid = 8821398 }}</ref> However, it should be noted that the activity of Beta 1, 3-D glucan is different from agents that stimulate the immune system. Agents that stimulate the immune system can push the system to over-stimulation, and hence are contraindicated in individuals with autoimmune diseases, allergies, or yeast infections. Beta 1, 3-D glucans seem to make the immune system work better without becoming overactive. They accomplish this by activating [[phagocytes]], which are immune system cells whose function is to trap and destroy foreign substances in our bodies such as bacteria, viruses, fungi, and parasites.<ref>{{cite journal
| last = Chihara | first = G | year = 1992 | title = Recent progress in immunopharmacology and therapeutic effects of polysaccharides | journal = Developments in biological standardization | volume = 77 | pages = 191-197 | publisher = [[Karger]] | location = Switzerland | issn = 0301-5149 | pmid = 1426662 }}</ref> In addition to enhancing the activity of phagocytes, beta-1,3 glucans also reportedly lower elevated levels of LDL cholesterol, aid in wound healing, help prevent infections, enhance NK cell function, and help in the prevention and treatment of cancer.


==Clinical Applications (conclusions of investigators)==
==Clinical Applications==


===Cancer===
'''· Cancer:''' β-Glucan has been used as an immunoadjuvant therapy for cancer since 1980, primarily in Japan. Numerous studies report that beta-1, 3 glucan has anti-tumor and anti-cancer activity.[5] [6] In one study, intralesional administration of beta-1,3 glucans resulted in rapid tumor shrinkage.[7] In another study with mice, beta 1,3 glucan in conjunction with interferon gamma inhibited both the establishment of tumors and liver metastasis.[8] In some studies, beta-1,3 glucans enhanced the effects of chemotherapy. In studies on bladder cancer with mice, administration of cyclophosphamide, in conjunction with beta-1,3 glucans derived from yeast resulted in reduced mortality.[9] In human patients with advanced gastric or colorectal cancer, the administration of beta-1,3 glucans derived from shiitake mushrooms, in conjunction with chemotherapy resulted in prolonged survival times compared to a control group receiving identical chemotherapy.[10]


β-Glucan has been used as an immuno[[wikt:adjuvant|adjuvant]] therapy for cancer since 1980, primarily in Japan. Numerous studies report that beta-1, 3 glucan has anti-tumor and anti-cancer activity.<ref>{{cite journal | last = DiLuzio | first = NR | coauthors = Williams DL, McNamee RB, Malshet VG | year = 1980 | title = Comparative evaluation of the tumor inhibitory and antibacterial activity of solubilized and particulate glucan | journal = Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer | volume = 75 | pages = 165-172 | publisher = [[Springer Verlag]] | location = Germany | issn = 0080-0015 | pmid = 7232829 }}</ref><ref>{{cite journal | last = Morikawa | first = K | coauthors = Takeda R, Yamazaki M, Mizuno D | year = 1985 | month = April | title = Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear beta-1,3-D-glucan and other immunomodulators in murine cells | journal = Cancer research | volume = 45 | issue = 4 | pages = 1496-1501 | publisher = [[American Association for Cancer Research]] | location = United States | issn = 0008-5472 | pmid = 3156669 }}</ref> In one study, intralesional administration of beta-1,3 glucans resulted in rapid tumor shrinkage.<ref>{{cite journal | last = Mansell | first = PW | coauthors = Ichinose H, Reed RJ, Krementz ET, McNamee R, Di Luzio NR | year = 1975 | month = March | title = Macrophage-mediated destruction of human malignant cells in vivo | journal = Journal of the National Cancer Institute | volume = 54 | issue = 3 | pages = 571-580 | publisher = [[Oxford University Press]] | location = United States | issn = 0027-8874 | pmid = 1123850 }}</ref> In another study with mice, beta 1,3 glucan in conjunction with interferon gamma inhibited both the establishment of tumors and liver metastasis.<ref>{{cite journal | last = Sveinbjørnsson | first = B | coauthors = Rushfeldt C, Seljelid R, Smedsrød B | year = 1998 | month = May | title = Inhibition of establishment and growth of mouse liver metastases after treatment with interferon gamma and beta-1,3-D-glucan | journal = Hepatology (Baltimore, Md.) | volume = 27 | issue = 5 | pages = 1241-1248 | publisher = [[John Wiley & Sons|Wiley]] | location = United States | issn = 0270-9139 | pmid = 9581677 }}</ref> In some studies, beta-1,3 glucans enhanced the effects of chemotherapy. In studies on bladder cancer with mice, administration of cyclophosphamide, in conjunction with beta-1,3 glucans derived from yeast resulted in reduced mortality.<ref>{{cite journal | last = Thompson | first = IM | coauthors = Spence CR, Lamm DL, DiLuzio NR | year = 1987 | month = Nov | title = Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide | journal = The American journal of the medical sciences | volume = 294 | issue = 5 | pages = 294-300 | publisher = [[Lippincott Williams & Wilkins]] | location = United States | issn = 0002-9629 | pmid = 3425579 }}</ref> In human patients with advanced gastric or colorectal cancer, the administration of beta-1,3 glucans derived from shiitake mushrooms, in conjunction with chemotherapy resulted in prolonged survival times compared to a control group receiving identical chemotherapy.<ref>{{cite journal | last = Wakui | first = A | coauthors = Kasai M, Konno K, Abe R, Kanamaru R, Takahashi K, Nakai Y, Yoshida Y, Koie H, Masuda H, et al. | year = 1986 | month = April | title = Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group | journal = Gan to kagaku ryoho. Cancer & chemotherapy | volume = 13 | issue = 4 pt 1 | pages = 1050-1059 | publisher = Gan To Kagaku Ryohosha | location = Japan | issn = 0385-0684 | pmid = 3083785 | language = Japanese }}</ref>

Preclinical studies have shown that a soluble yeast β-glucan product, Imprime PGG, when used in combination with certain monoclonal antibodies or cancer vaccines, offers significant improvements in long-term survival versus monoclonal antibodies alone.[11] This benefit, however, does not result from [[Betafectin]] enhancing the specific killing action of the antibody. The anti-tumor activity is caused by a unique killing mechanism that involves [[neutrophils]] that are primed with Betafectin and which are not normally involved in the fight against cancer.[11][12] Recent research by Hong et al, demonstrates that this mechanism of action is effective against a broad range of cancers when used in combination with specific monoclonal antibodies that activate or cause [[complement]] to be bound to the tumor.[13] The complement enables these primed neutrophils to find and bind to the tumor, which facilitates killing. Innate immune cells are the body’s first line of defense and circulate throughout the body engaging in an immune response against “foreign” challenges (bacteria, fungus, parasites). Typically, neutrophils are not involved in the destruction of cancerous tissue because these immune cells view cancer as "self" rather than foreign or "non-self." Current cancer immunotherapies involve monoclonal antibodies and vaccines, which stimulate the acquired immune response, but do nothing to change the innate immune system's view of cancer as "self." As a result the monoclonal antibodies alone do not engage or initiate the potential killing ability of the innate immune system, which is our primary mechanism of defense against bacteria and yeast (fungal) infections.
Preclinical studies have shown that a soluble yeast β-glucan product, Imprime PGG, when used in combination with certain monoclonal antibodies or cancer vaccines, offers significant improvements in long-term survival versus monoclonal antibodies alone.<ref name="Vetvicka">{{cite journal | last = Vetvicka | first = V | coauthors = Thornton BP, Ross GD | date = [[1996-07-01]] | title = Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells | journal = The Journal of clinical investigation | volume = 98 | issue = 1 | pages = 50-61 | publisher = American Society for Clinical Investigation | location = United States | issn = 0021-9738 | pmid = 8690804 }}</ref> This benefit, however, does not result from [[Betafectin]] enhancing the specific killing action of the antibody. The anti-tumor activity is caused by a unique killing mechanism that involves [[neutrophils]] that are primed with Betafectin and which are not normally involved in the fight against cancer.<ref name="Vetvicka"/><ref name="Hong 04">{{cite journal | last = Hong | first = F | coauthors = Yan J, Baran JT, Allendorf DJ, Hansen RD, Ostroff GR, Xing PX, Cheung NK, Ross GD | date = [[2004-07-15]] | title = Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models | journal = Journal of immunology (Baltimore, Md. : 1950) | volume = 173 | issue = 2 | pages = 797-806 | publisher = American Association of Immunologists | location = United States | issn = 0022-1767 | pmid = 15240666 }}</ref> Recent research by Hong et al, demonstrates that this mechanism of action is effective against a broad range of cancers when used in combination with specific monoclonal antibodies that activate or cause [[complement]] to be bound to the tumor.<ref>{{cite journal | last = Hong | first = F | coauthors = Hansen RD, Yan J, Allendorf DJ, Baran JT, Ostroff GR, Ross GD | date = [[2003-12-15]] | title = Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells | journal = Cancer research | volume = 63 | issue = 24 | pages = 9023-9031 | publisher = [[American Association for Cancer Research]] | location = United States | issn = 0008-5472 | pmid = 14695221 }}</ref> The complement enables these primed neutrophils to find and bind to the tumor, which facilitates killing. Innate immune cells are the body’s first line of defense and circulate throughout the body engaging in an immune response against “foreign” challenges (bacteria, fungus, parasites). Typically, neutrophils are not involved in the destruction of cancerous tissue because these immune cells view cancer as "self" rather than foreign or "non-self." Current cancer immunotherapies involve monoclonal antibodies and vaccines, which stimulate the acquired immune response, but do nothing to change the innate immune system's view of cancer as "self." As a result the monoclonal antibodies alone do not engage or initiate the potential killing ability of the innate immune system, which is our primary mechanism of defense against bacteria and yeast (fungal) infections.


Dr. Gordon Ross and Dr. Vaclav Vetvicka, respected immunologists and cancer researchers at the University of Louisville, discovered that a receptor on the surface of these innate immune cells called [[Complement Receptor 3]] ([[Complement receptor 3| CR3]] or CD11b/[[CD18]]) was responsible for binding to fungi or yeast, allowing the immune cells to recognize them as "non-self."[11] This receptor is a dual occupancy receptor in that it has two binding sites. The first site is responsible for binding to a type of complement, a soluble blood protein, known as [[C3]] (or iC3b). C3 becomes attached to pathogens that specific antibodies have targeted and opsonized. The second site of this receptor binds to a carbohydrate on yeast or fungal cells that allows the innate immune cell to recognize yeast and fungi as being "non-self ”.[12][14] Both of these receptor sites must be simultaneously occupied to trigger the innate immune cell to destroy the yeast or fungi. Two obstacles prevent neutrophils from using this mechanism of action against cancer. First, the body usually does not generate enough natural antibodies to bind to the tumor, and this prevents the activation and attachment of (or “fixing”) complement to the surface of the cancer cell. Therefore, neutrophils don’t bind to cancer via the first receptor site of CR3. The second obstacle is that even when the natural antibody response is supplemented with monoclonal antibodies that fix complement and binding occurs at the first site, tumors do not contain a foreign carbohydrate serving as “second signal” on their surface that allows neutrophils to recognize the cancer as "non-self “.[12][15]
Dr. Gordon Ross and Dr. Vaclav Vetvicka, respected immunologists and cancer researchers at the University of Louisville, discovered that a receptor on the surface of these innate immune cells called [[Complement Receptor 3]] ([[Complement receptor 3| CR3]] or CD11b/[[CD18]]) was responsible for binding to fungi or yeast, allowing the immune cells to recognize them as "non-self."<ref name="Vetvicka"> This receptor is a dual occupancy receptor in that it has two binding sites. The first site is responsible for binding to a type of complement, a soluble blood protein, known as [[C3]] (or iC3b). C3 becomes attached to pathogens that specific antibodies have targeted and opsonized. The second site of this receptor binds to a carbohydrate on yeast or fungal cells that allows the innate immune cell to recognize yeast and fungi as being "non-self ”.<ref name="Hong 04"/><ref>{{cite journal | last = Thornton | first = BP | coauthors = Vĕtvicka V, Pitman M, Goldman RC, Ross GD | date = [[1996-02-01]] | title = Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18) | journal = Journal of immunology (Baltimore, Md. : 1950) | volume = 156 | issue = 3 | pages = 1235-1246 | publisher = American Association of Immunologists | location = United States | issn = 0022-1767 | pmid = 8558003 }}</ref> Both of these receptor sites must be simultaneously occupied to trigger the innate immune cell to destroy the yeast or fungi. Two obstacles prevent neutrophils from using this mechanism of action against cancer. First, the body usually does not generate enough natural antibodies to bind to the tumor, and this prevents the activation and attachment of (or “fixing”) complement to the surface of the cancer cell. Therefore, neutrophils don’t bind to cancer via the first receptor site of CR3. The second obstacle is that even when the natural antibody response is supplemented with monoclonal antibodies that fix complement and binding occurs at the first site, tumors do not contain a foreign carbohydrate serving as “second signal” on their surface that allows neutrophils to recognize the cancer as "non-self “.<ref name="Hong 04"><ref>{{cite journal | last = Gelderman | first = KA | coauthors = Tomlinson S, Ross GD, Gorter A | year = 2004 | month = March | title = Complement function in mAb-mediated cancer immunotherapy | journal = Trends in immunology | volume = 25 | issue = 3 | pages = 158-164 | publisher = [[Elsevier Science]] | location = England | issn = 1471-4906 | pmid = 15036044 }}</ref>


Dr. Ross discovered that a bio-processed fragment of Imprime PGG specifically binds to the second CR3 receptor site on neutrophils. When neutrophils bind to tumors, the Betafectin allows them to “see” cancer as if it were a yeast or fungal pathogen and provide the “second signal” to trigger killing. In summary, Betafectin engages neutrophils in the fight against cancer, dramatically and synergistically enhancing the effectiveness of complement activating monoclonal antibodies and vaccines through a different killing mechanism.
Dr. Ross discovered that a bio-processed fragment of Imprime PGG specifically binds to the second CR3 receptor site on neutrophils. When neutrophils bind to tumors, the Betafectin allows them to “see” cancer as if it were a yeast or fungal pathogen and provide the “second signal” to trigger killing. In summary, Betafectin engages neutrophils in the fight against cancer, dramatically and synergistically enhancing the effectiveness of complement activating monoclonal antibodies and vaccines through a different killing mechanism.


Multinational research has successfully demonstrated that the oral form of yeast Beta 1,3-D glucan has similar protective effects as the injected version, including defense against infectious diseases and cancer.<ref name="Pilot Study">{{cite journal | last = Vetvicka | first = V | coauthors = Terayama K, Mandeville R, Brousseau P, Kournikakis B, Ostroff G | year = 2002 | title = Pilot Study: Orally-Administered Yeast β1,3-glucan Prophylactically Protects Against Anthrax Infection and Cancer in Mice | journal = Journal of the American Nutraceutical Association | volume = 5 | issue = 2 | pages = 5-9 | publisher = Birmingham, AL : The Association | url = http://www.ana-jana.org/Journal/journals/JANAVol52.pdf | issn = 1521-4524 }}</ref><ref>{{cite journal | last = Fujimoto | first = S | year = 1989 | month = September | title = Clinical efficacies of schizophyllan (SPG) on advanced gastric cancer | journal = Nippon Geka Gakkai Zasshi | volume = 90 | issue = 9 | pages = 1447-1450 | publisher = Nippon Geka Gakkai | location = Japan | issn = 0301-4894 | pmid = 2531270 | language = Japanese }}</ref><ref>{{cite journal | last = Hanaue | first = H | coauthors = Tokuda Y, Machimura T, Kamijoh A, Kondo Y, Ogoshi K, Makuuchi H, Nakasaki H, Tajima T, Mitomi T, et al. | year = 1989 | month = Sep-Oct | title = Effects of oral lentinan on T-cell subsets in peripheral venous blood. | journal = Clinical therapeutics | volume = 11 | issue = 5 | pages = 614-622 | publisher = Excerpta Medica | location = United States | issn = 0149-2918 | pmid = 2529966 }}</ref><ref>{{cite journal | last = Rice | first = PJ | coauthors = Adams EL, Ozment-Skelton T, Gonzalez AJ, Goldman MP, Lockhart BE, Barker LA, Breuel KF, Deponti WK, Kalbfleisch JH, Ensley HE, Brown GD, Gordon S, Williams DL | year = 2005 | month = September | title = Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge | journal = The Journal of pharmacology and experimental therapeutics | volume = 314 | issue = 3 | pages = 1079-1086 | publisher = [[American Society for Pharmacology and Experimental Therapeutics]] | location = United States | issn = 0022-3565 | pmid = 15976018 }}</ref><ref>{{cite journal | last = Suzuki | first = I | coauthors = Hashimoto K, Ohno N, Tanaka H, Yadomae T | year = 1989 | title = Immunomodulation by orally administered beta-glucan in mice | journal = >International journal of immunopharmacology | volume = 11 | issue = 7 | pages = 761-769 | publisher = [[Elsevier Science]] | location = England | issn = 0192-0561 | pmid = 2599714 }}</ref> Recently, orally-delivered glucan was found to significantly increase proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer.<ref>{{cite journal | last = Demir | first = G | coauthors = Klein HO, Mandel-Molinas N, Tuzuner N | year = 2007 | month = January | title = Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer | journal = International immunopharmacology | volume = 7 | issue = 1 | pages = 113-116 | publisher = [[Elsevier Science]] | location = Netherlands | issn = 1567-5769 | pmid = 17161824 }}</ref>
Multinational research has successfully demonstrated that the oral form of yeast Beta 1,3-D glucan has similar protective effects as the injected version, including defense against infectious diseases and cancer.[16][17][18][19][20] Recently, orally-delivered glucan was found to significantly increase proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer.[21]


The technology has wide applicability for cancer therapy. Each form of cancerous tumor cell has specific antigens on the cell surface, some of which are common to other types of cancer. (Example: [[Mucin 1]] is present on about 70% of all types of cancer cells) Different immunotherapies target different antigens for binding monoclonal antibodies to tumor cells. This has resulted in the development of hundreds of monoclonal antibodies, many targeting a different specific antigen on cancer cells. In research studies, Betafectin has improved the effectiveness of all complement-activating monoclonal antibodies tested including breast, liver and lung cancer (company data). The magnitude of success varies based on the specific monoclonal antibody used and the type of cancer.
The technology has wide applicability for cancer therapy. Each form of cancerous tumor cell has specific antigens on the cell surface, some of which are common to other types of cancer. (Example: [[Mucin 1]] is present on about 70% of all types of cancer cells) Different immunotherapies target different antigens for binding monoclonal antibodies to tumor cells. This has resulted in the development of hundreds of monoclonal antibodies, many targeting a different specific antigen on cancer cells. In research studies, Betafectin has improved the effectiveness of all complement-activating monoclonal antibodies tested including breast, liver and lung cancer (company data). The magnitude of success varies based on the specific monoclonal antibody used and the type of cancer.


===Prevention of infection===
'''· Prevention of infection:''' To date there have been numerous studies and clinical trials conducted with the soluble yeast β-glucan and the whole glucan particulate. These studies have ranged from the impact of β-glucan on post-surgical nosocomial infections to the role of yeast β-glucans in treating anthrax infections.


To date there have been numerous studies and clinical trials conducted with the soluble yeast β-glucan and the whole glucan particulate. These studies have ranged from the impact of β-glucan on post-surgical nosocomial infections to the role of yeast β-glucans in treating anthrax infections.
Post-surgical infections are a serious challenge following major surgery with estimates of 25-27% infection rates post-surgery.[22] Alpha-Beta Technologies conducted a series of human clinical trials in the 1990’s to evaluate the impact of β-glucan therapy for controlling infections in high-risk surgical patients.[22] In the initial trial 34 patients were randomly (double-blind, placebo-controlled) assigned to treatment or placebo groups. Patients that 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 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.


Post-surgical infections are a serious challenge following major surgery with estimates of 25-27% infection rates post-surgery.<ref name=babineau>{{cite journal | last = Babineau | first = TJ | coauthors = Marcello P, Swails W, Kenler A, Bistrian B, Forse RA | year = 1994 | month = November | title = Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients | journal = Annals of surgery | volume = 220 | issue = 5 | pages = 601-609 | publisher = [[Lippincott Williams & Wilkins]] | location = United States | issn = 0003-4932 | pmid = 7979607 }}</ref> Alpha-Beta Technologies conducted a series of human clinical trials in the 1990’s to evaluate the impact of β-glucan therapy for controlling infections in high-risk surgical patients.<ref name=babineau/> In the initial trial 34 patients were randomly (double-blind, placebo-controlled) assigned to treatment or placebo groups. Patients that 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 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 [23] further studied the impact of β-glucan for reducing the incidence of infection with high-risk surgical patients. The authors found a similar result with a dose-response trend (higher dose provided greater reduction in infectious occurrences than low doses). In the human clinical trial 67 patients were randomized and received either a placebo or a dose of 0.1, 0.5, 1.0 or 2.0 mg PGG-Glucan per KG of body weight. Serious infections occurred in four patients that received the placebo, three patients that received the low dose (0.1 mg/KG) of PGG-Glucan and only one infection was observed at the highest dose of 2.0 mg/KG of PGG-Glucan.


A subsequent human clinical trial <ref>{{cite journal | last = Babineau | first = TJ | coauthors = Hackford A, Kenler A, Bistrian B, Forse RA, Fairchild PG, Heard S, Keroack M, Caushaj P, Benotti P | year = 1994 | month = November | title = A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients | journal = Archives of surgery (Chicago, Ill. : 1960) | volume = 129 | issue = 11 | pages = 1204-1210 | publisher = [[American Medical Association]] | location = United States | issn = 0004-0010 | pmid = 7979954 }}</ref> further studied the impact of β-glucan for reducing the incidence of infection with high-risk surgical patients. The authors found a similar result with a dose-response trend (higher dose provided greater reduction in infectious occurrences than low doses). In the human clinical trial 67 patients were randomized and received either a placebo or a dose of 0.1, 0.5, 1.0 or 2.0 mg PGG-Glucan per KG of body weight. Serious infections occurred in four patients that received the placebo, three patients that received the low dose (0.1 mg/KG) of PGG-Glucan and only one infection was observed at 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.[24] 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.


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.<ref name=dellinger>{{cite journal | last = Dellinger | first = EP | coauthors = Babineau TJ, Bleicher P, Kaiser AB, Seibert GB, Postier RG, Vogel SB, Norman J, Kaufman D, Galandiuk S, Condon RE | year = 1999 | month = September | title = Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group | journal = Archives of surgery (Chicago, Ill. : 1960) | volume = 134 | issue = 9 | pages = 977-983 | publisher = [[American Medical Association]] | location = United States | issn = 0004-0010 | pmid = 10487593 }}</ref> 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.
At this point in the development of an injectable form of b-glucan (Betafectin [[PGG-glucan]]) most scientists already concluded that yeast-derived b-glucan promoted phagocytosis and subsequent killing of pathogenic bacteria. 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. The results of the phase III human clinical trial showed that injectable PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations.[25]

At this point in the development of an injectable form of b-glucan (Betafectin [[PGG-glucan]]) most scientists already concluded that yeast-derived b-glucan promoted phagocytosis and subsequent killing of pathogenic bacteria. 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. The results of the phase III human clinical trial showed that injectable PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations.<ref name=dellinger/>


There have been studies with humans and animal models that further support the efficacy of β-glucan in combating various infectious diseases. One human study demonstrated that consumption of oral whole glucan particles increased the ability of immune cells to consume a bacterial challenge (phagocytosis). The total number of phagocytic cells and the efficiency of phagocytosis in healthy human study participants increased while consuming a commercial particulate yeast β-glucan. This study demonstrated the potential for yeast β-glucan to increase the reaction rate of the immune system to infectious challenges. The study concluded that oral consumption of whole glucan particles represented a good enhancer of natural immunity.
There have been studies with humans and animal models that further support the efficacy of β-glucan in combating various infectious diseases. One human study demonstrated that consumption of oral whole glucan particles increased the ability of immune cells to consume a bacterial challenge (phagocytosis). The total number of phagocytic cells and the efficiency of phagocytosis in healthy human study participants increased while consuming a commercial particulate yeast β-glucan. This study demonstrated the potential for yeast β-glucan to increase the reaction rate of the immune system to infectious challenges. The study concluded that oral consumption of whole glucan particles represented a good enhancer of natural immunity.


[[Anthrax]] is a disease that cannot be tested in human studies for obvious reasons. In a study conducted by the Canadian Department of Defense, Dr. Kournikakis showed that orally administered yeast β-glucan given with or without antibiotics protected mice against anthrax infection.[16] 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.
[[Anthrax]] is a disease that cannot be tested in human studies for obvious reasons. In a study conducted by the Canadian Department of Defense, Dr. Kournikakis showed that orally administered yeast β-glucan given with or without antibiotics protected mice against anthrax infection.<ref name="Pilot Study"/> 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. The hopeful inference is that similar results would be observed with humans.
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. The hopeful inference is that similar results would be observed with humans.


Since there are many commercial products on the market called “glucan”, there is much confusion among consumers as to which type(s) may be the most effective. One of the most comprehensive published studies to date showed Glucan #300, a highly purified yeast glucan, to be “the biologically most relevant immunomodulator” out of a wide ranging group.[26]
Since there are many commercial products on the market called “glucan”, there is much confusion among consumers as to which type(s) may be the most effective. One of the most comprehensive published studies to date showed Glucan #300, a highly purified yeast glucan, to be “the biologically most relevant immunomodulator” out of a wide ranging group.<ref>{{cite journal | last = Vetvicka | first = V | coauthors = Vetvickova J | year = 2007 | title = An Evaluation of the Immunological Activities of Commercially Available β1, 3-Glucans | journal = Journal of the American Nutraceutical Association | volume = 10 | issue = 1 | pages = 25-31 | publisher = Birmingham, AL : The Association | location = | issn = 1521-4524 | url = http://www.ana-jana.org/Journal/journals/JANAvol1no12007forinternet.pdf }}</ref>
===Radiation exposure===


'''· Radiation exposure:''' β-glucan is a well-known biological response modifier (BRM) isolated from the yeast cell wall polysaccharides and is made up entirely of glucose β(1,3)-linked together in linear chains with variable frequency of β(1,6)-linked side chains.[27] 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).[28]Research was carried out initially with particulate β-glucan and later with soluble β-glucans, all of which were administered intravenously to mice.[29][30][31]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.[32] Other reports showed that β-glucan could reverse the myelo-suppression produced with chemotherapeutic drugs such as fluorouracil,[24] carboplatinum or cyclophosphamide.[33] 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.[22] 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.[34]
β-glucan is a well-known biological response modifier (BRM) isolated from the yeast cell wall polysaccharides and is made up entirely of glucose β(1,3)-linked together in linear chains with variable frequency of β(1,6)-linked side chains.<ref>{{cite book|last= Stone|first= Bruce A.|coauthors= Clarke, Adrienne E.|title=Chemistry and Biology of (1→3)-β-Glucans|year=1993|month=January|publisher=La Trobe University Press|location=[[Victoria (Australia)|Victoria]], [[Australia]]|isbn=978-1863244091}}</ref> 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).<ref>{{cite journal | last = Patchen | first = ML | coauthors = MacVittie TJ | year = 1983 | month = April | title = Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan | journal = Immunopharmacology | volume = 5 | issue = 4 | pages = 303-313 | publisher = Elsevier/North-Holland | location = Netherlands | issn = 0162-3109 | pmid = 6853144 }}</ref> Research was carried out initially with particulate β-glucan and later with soluble β-glucans, all of which were administered intravenously to mice.<ref>{{cite journal | last = Patchen | first = ML | coauthors = DiLuzio NR, Jacques P, MacVittie TJ | year = 1984 | month = December | title = Soluble polyglycans enhance recovery from cobalt-60--induced hemopoietic injury | journal = Journal of biological response modifiers | volume = 3 | issue = 6 | pages = 627-633 | publisher = Raven Press | location = United States | issn = 0732-6580 | pmid = 6512563 }}</ref><ref>{{cite journal | last = Patchen | first = ML | coauthors = MacVittie TJ, Wathen LM | date = [[1984-11-15]] | title = Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells | journal = Experientia | volume = 40 | issue = 11 | pages = 1240-1244 | publisher = Birkhäuser Verlag | location = Switzerland | issn = 0014-4754 | pmid = 6500009 }}</ref><ref>{{cite journal | last = Petruczenko | first = A | year = 1984 | month = May-June | title = Glucan effect on the survival of mice after radiation exposure | journal = Acta physiologica Polonica | volume = 35 | issue = 3 | pages = 231-236 | publisher = Panstwowy Zaklad Wydawnictw Lekarskich | location = Poland | issn = 0044-6033 | pmid = 6537716 }}</ref> 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.<ref>{{cite journal | last = Patchen | first = ML | coauthors = MacVittie TJ | year = 1986 | month = February | title = Comparative effects of soluble and particulate glucans on survival in irradiated mice | journal = Journal of biological response modifiers | volume = 5 | issue = 1 | pages = 45-60 | publisher = Raven Press | location = United States | issn = 0732-6580 | pmid = 3958754 }}</ref> Other reports showed that β-glucan could reverse the myelo-suppression produced with chemotherapeutic drugs such as fluorouracil,<ref name=dellinger/> carboplatinum or cyclophosphamide.<ref>{{cite journal | last = Patchen | first = ML | coauthors = Vaudrain T, Correira H, Martin T, Reese D | year = 1998 | month = December | title = In vitro and in vivo hematopoietic activities of Betafectin PGG-glucan. | journal = Experimental hematology | volume = 26 | issue = 13 | pages = 1247-1254 | publisher = [[Elsevier Science]] | location = Netherlands | issn = 0301-472X | pmid = 9845381 }}</ref> 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.<ref name=babineau/> 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.<ref>{{cite journal | last = Turnbull | first = JL | coauthors = Patchen ML, Scadden DT | year = 1999 | title = The polysaccharide, PGG-glucan, enhances human myelopoiesis by direct action independent of and additive to early-acting cytokines | journal = Acta haematologica | volume = 102 | issue = 2 | pages = 66-71 | publisher = Karger | location = Switzerland | issn = 0001-5792 | pmid = 10529508 }}</ref>


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,[12][35][36][37]opening the oral route of administration as a more pleasant alternative. A study by Allendorf et al.[38] 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.[36] 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.[39] or Vetvicka [36] clearly demonstrated that oral β-glucan stimulates hematopoiesis in radiation-treated mice. Currently, there is renewed interest in the potential usefulness of β-glucan as a radioprotective drug for chemotherapy, radiation therapy and nuclear emergencies, particularly because glucan can be used not only as a treatment, but also as a prophylactic.
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,<ref name="Hong 04"/><ref>{{cite journal | last = Tomoda | first = M | coauthors = Ohara N, Shimizu N, Gonda R | year = 1994 | month = March | title = Characterization of a novel glucan, which exhibits reticuloendothelial system-potentiating and anti-complementary activities, from the rhizome of Cnidium officinale | journal = Chemical & pharmaceutical bulletin | volume = 42 | issue = 3 | pages = 630-633 | publisher = Pharmaceutical Society of Japan | location = Japan | issn = 0009-2363 | pmid = 8004712 }}</ref><ref name="Vetvicka orally">{{cite journal | last = Vetvicka | first = V | coauthors = Dvorak B, Vetvickova J, Richter J, Krizan J, Sima P, Yvin JC | date = [[2007-03-10]] | title = Orally administered marine (1-->3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity. | journal = International journal of biological macromolecules | volume = 40 | issue = 4 | pages = 291-298 | publisher = [[Butterworth-Heinemann]] | location = England | issn = 0141-8130 | pmid = 16978690 }}</ref><ref>{{cite journal | last = Mucksová | first = J | coauthors = Babícek K, Pospísil M | year = 2001 | title = Particulate 1,3-beta-D-glucan, carboxymethylglucan and sulfoethylglucan--influence of their oral or intraperitoneal administration on immunological respondence of mice. | journal = Folia microbiologica | volume = 46 | issue = 6 | pages = 559-563 | publisher = Slovak Academy Of Sciences | location = Czech Republic | issn = 0015-5632 | pmid = 11898349 }}</ref> opening the oral route of administration as a more pleasant alternative. A study by Allendorf et al.<ref>Oral WGP Beta Glucan Treatment Accelerates Myeloid Recovery after Radiation Exposure. Presented at [http://www.btr-albuquerque.org BTR 2003]</ref> 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.<ref name="Vetvicka orally"/> 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.<ref>{{cite journal | last = Cramer | first = DE | coauthors = Allendorf DJ, Baran JT, Hansen R, Marroquin J, Li B, Ratajczak J, Ratajczak MZ, Yan J | date = [[2006-01-15]] | title = Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury | journal = Blood | volume = 107 | issue = 2 | pages = 835-840 | publisher = [[American Society of Hematology]] | location = United States | issn = 0006-4971 | pmid = 16179370 }}</ref> or Vetvicka <ref name="Vetvicka orally"/> clearly demonstrated that oral β-glucan stimulates hematopoiesis in radiation-treated mice. Currently, there is renewed interest in the potential usefulness of β-glucan as a radioprotective drug for chemotherapy, radiation therapy and nuclear emergencies, particularly because glucan can be used not only as a treatment, but also as a prophylactic.


===Septic shock===
'''· Septic shock:''' One of the mechanisms of the immune-enhancing ability of yeast β-glucan is its ability to prime leukocytes to more easily locate and kill non-self cells including bacteria. Early research by Onderdonk et al.[40] 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&ndash;6 hours prior to infection. Additional research further supports that yeast β-glucan reduces septic shock by killing bacteria present in blood. 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. [41] Research on the use of yeast β-glucan immunomodulators as a means of treating and preventing bacterial sepsis is well documented.[40][41][42] Recent reports on glucan and sepsis revealed another possible mechanism - glucan protects against oxidative organ injury.[43]


One of the mechanisms of the immune-enhancing ability of yeast β-glucan is its ability to prime leukocytes to more easily locate and kill non-self cells including bacteria. Early research by Onderdonk et al.<ref name=Onderdonk>{{cite journal | last = Onderdonk | first = AB | coauthors = Cisneros RL, Hinkson P, Ostroff G | year = 1992 | month = April | title = Anti-infective effect of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan in vivo. | journal = Infection and immunity | volume = 60 | issue = 4 | pages = 1642-1647 | publisher = [[American Society for Microbiology]] | location = United States | issn = 0019-9567 | pmid = 1548086 }}</ref> 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&ndash;6 hours prior to infection. Additional research further supports that yeast β-glucan reduces septic shock by killing bacteria present in blood. 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.<ref name=kernodle>{{cite journal | last = Kernodle | first = DS | coauthors = Gates H, Kaiser AB | year = 1998 | month = March | title = Prophylactic anti-infective activity of poly-[1-6]-beta-D-glucopyranosyl-[1-3]-beta-D-glucopryanose glucan in a guinea pig model of staphylococcal wound infection | journal = Antimicrobial agents and chemotherapy | volume = 42 | issue = 3 | pages = 545-549 | publisher = [[American Society for Microbiology]] | location = United States | issn = 0066-4804 | pmid = 9517930 }}</ref> Research on the use of yeast β-glucan immunomodulators as a means of treating and preventing bacterial sepsis is well documented.<ref name=Onderdonk/><ref name=kernodle/><ref>{{cite journal | last = Tzianabos | first = AO | coauthors = Gibson FC 3rd, Cisneros RL, Kasper DL | year = 1998 | month = July | title = Protection against experimental intraabdominal sepsis by two polysaccharide immunomodulators. | journal = The Journal of infectious diseases | volume = 178 | issue = 1 | pages = 200-206 | publisher = [[University of Chicago Press]] | location = United States | issn = 0022-1899 | pmid = 9652441 }}</ref> Recent reports on glucan and sepsis revealed another possible mechanism - glucan protects against oxidative organ injury.<ref>{{cite journal | last = Sener | first = G | coauthors = Toklu H, Ercan F, Erkanli G | year = 2005 | month = August | title = Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis | journal = International immunopharmacology | volume = 5 | issue = 9 | pages = 1387-1396 | publisher = [[Elsevier Science]] | location = Netherlands | issn = 1567-5769 | pmid = 15953565 }}</ref>
'''· Surgery:''' There have been numerous studies and clinical trials conducted with the soluble yeast β-glucan particle and the whole glucan particle. Immunomodulators that enhance macrophage function have been shown to be beneficial in human, as well as, animal models. One such study that looked at this correlation examined wound tensile strength and collagen biosynthesis. Positive effects were observed.[44]


===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%). Further such trials to evaluate Biological Response Modifiers (BRM’s) in trauma patients are indicated.[45]


There have been numerous studies and clinical trials conducted with the soluble yeast β-glucan particle and the whole glucan particle. Immunomodulators that enhance macrophage function have been shown to be beneficial in human, as well as, animal models. One such study that looked at this correlation examined wound tensile strength and collagen biosynthesis. Positive effects were observed.<ref>{{cite journal | last = Portera | first = CA | coauthors = Love EJ, Memore L, Zhang L, Müller A, Browder W, Williams DL | year = 1997 | month = February | title = Effect of macrophage stimulation on collagen biosynthesis in the healing wound | journal = The American surgeon | volume = 63 | issue = 2 | pages = 125-131 | publisher = Southeastern Surgical Congress | location = United States | issn = 0003-1348 | pmid = 9012425 }}</ref>
Yeast derived beta glucan significantly enhanced phagocytic activity in control and operated mice. In an experimental C. albicans model, mice had induced sepsis along with a midline [[laparotomy]]. The non-operated mice on glucan had a 100% survival vs. 73% in the surgical group. Detrimental effects of surgery on survival of C. albicans infection manifested in a 47% survival in the non-surgical vs a 20% survival in the surgery-infected group.[46]


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%). Further such trials to evaluate Biological Response Modifiers (BRM’s) in trauma patients are indicated.<ref>{{cite journal | last = Browder | first = W | coauthors = Williams D, Pretus H, Olivero G, Enrichens F, Mao P, Franchello A | year = 1990 | month = May | title = Beneficial effect of enhanced macrophage function in the trauma patient | journal = Annals of surgery | volume = 211 | issue = 5 | pages = 605-612; discussion 612-613 | publisher = [[Lippincott Williams & Wilkins]] | location = United States | issn = 0003-4932 | pmid = 2111126 }}</ref>
The nonspecific immunostimulation of yeast derived glucan appears to have significant potential as a treatment strategy against post-operative infections. In a post splenectomy mouse model, glucan increased survival vs. controls via 75% as opposed to 27%, Severe sepsis enhances risks in both adult and pediatric patients. These works suggest another option beyond prophylactic antibiotics and bacterial vaccines that often have limited success against morbidity and mortality.[47]


Yeast derived beta glucan significantly enhanced phagocytic activity in control and operated mice. In an experimental C. albicans model, mice had induced sepsis along with a midline [[laparotomy]]. The non-operated mice on glucan had a 100% survival vs. 73% in the surgical group. Detrimental effects of surgery on survival of C. albicans infection manifested in a 47% survival in the non-surgical vs a 20% survival in the surgery-infected group.<ref>{{cite journal | last = Browder | first = IW | coauthors = Williams DL, Kitahama A, Di Luzio NR | year = 1984 | title = Modification of post-operative C. albicans sepsis by glucan immunostimulation. | journal = International journal of immunopharmacology | volume = 6 | issue = 1 | pages = 19-26 | publisher = [[Elsevier Science]] | location = England | issn = 0192-0561 | pmid = 6724765 }}</ref>
'''· Wound healing:''' Macrophage activity is known to play a key role in wound healing from surgery or trauma. In both animal and human studies, therapy with Beta glucan has provided improvements such as fewer infections, reduced mortality, and stronger tensile strength of scar tissue.


The nonspecific immunostimulation of yeast derived glucan appears to have significant potential as a treatment strategy against post-operative infections. In a post splenectomy mouse model, glucan increased survival vs. controls via 75% as opposed to 27%, Severe sepsis enhances risks in both adult and pediatric patients. These works suggest another option beyond prophylactic antibiotics and bacterial vaccines that often have limited success against morbidity and mortality.<ref name=kirmaz>{{cite journal | last = Kirmaz | first = C | coauthors = Bayrak P, Yilmaz O, Yuksel H. | year = 2005 | month = June | title = Effects of glucan treatment on the Th1/Th2 balance in patients with allergic rhinitis: a double-blind placebo-controlled study. | journal = European cytokine network | volume = 16 | issue = 2 | pages = 128-134 | publisher = John Libbey Eurotext | location = France | issn = 1148-5493 | pmid = 15941684 }}</ref>
'''· Allergic rhinitis:''' 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. Based on these studies, glucan may have a role as an adjunct to standard treatment in patients with allergic diseases.[48]


===Wound healing===
'''· 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.[49]

Macrophage activity is known to play a key role in wound healing from surgery or trauma. In both animal and human studies, therapy with Beta glucan has provided improvements such as fewer infections, reduced mortality, and stronger tensile strength of scar tissue.

===Allergic rhinitis===

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. Based on these studies, glucan may have a role as an adjunct to standard treatment in patients with allergic diseases.<ref name=kirmaz/>

===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.<ref>{{cite journal | last = Kogan | first = G | coauthors = Stasko A, Bauerova K, Polovka M, Soltes L, Brezova V, Navarova J | date = [[2005-07-04]] | title = Antioxidant properties of yeast (1→3)-β-d-glucan studied by electron paramagnetic resonance spectroscopy and its activity in the adjuvant arthritis | journal = Carbohydrate Polymers | volume = 61 | issue = 1 | pages = 18-28 | publisher = Elsevier | location = | issn = 0144-8617 | doi = 10.1016/j.carbpol.2005.02.010 }}</ref>
'''· Additional functions:''' 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 arteriosclerosis and heart disease hazards, is also mediated by b-glucan.[50] It is known that cereals, mushrooms and yeast facilitate bowel motility and can be used in amelioration of intestinal problems, particularly obstipation.[51][52] Non-digestible b-glucans, forming a remarkable portion of these materials, are also able to modulate mucosal immunity of the intestinal tract.[53] In the central nervous system, β-glucans activate microglial cells.[54] These cells act as scavengers of the brain cell debris and play a positive role in Alzheimer’s disease, AIDS, ischemia injury and multiple sclerosis.[55][56]

===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]] and [[cardiovascular disease]] hazards, is also mediated by b-glucans.<ref>{{cite journal | last = Keogh | first = GF | coauthors = Cooper GJ, Mulvey TB, McArdle BH, Coles GD, Monro JA, Poppitt SD | year = 2003 | month = October | title = Randomized controlled crossover study of the effect of a highly beta-glucan-enriched barley on cardiovascular disease risk factors in mildly hypercholesterolemic men | journal = The American journal of clinical nutrition | volume = 78 | issue = 4 | pages = 711-718 | publisher = American Society of Clinical Nutrition | location = United States | issn = 0002-9165 | pmid = 14522728 }}</ref> It is known that cereals, mushrooms and yeast facilitate bowel motility and can be used in amelioration of intestinal problems, particularly obstipation.<ref>{{cite journal | last = Dongowski | first = G | coauthors = Huth M, Gebhardt E, Flamme W | year = 2002 | month = December | title = Dietary fiber-rich barley products beneficially affect the intestinal tract of rats | journal = The Journal of nutrition | volume = 132 | issue = 12 | pages = 3704-3714 | publisher = American Society of Nutritional Sciences | location = United States | issn = 0022-3166 | pmid = 12468611 }}</ref><ref>{{cite journal | last = Battilana | first = P | coauthors = Ornstein K, Minehira K, Schwarz JM, Acheson K, Schneiter P, Burri J, Jéquier E, Tappy L | year = 2001 | month = May | title = Mechanisms of action of beta-glucan in postprandial glucose metabolism in healthy men. | journal = European journal of clinical nutrition | volume = 55 | issue = 5 | pages = 327-333 | publisher = [[Nature Publishing Group]] | location = England | issn = 0954-3007 | pmid = 11378805 }}</ref> Non-digestible b-glucans, forming a remarkable portion of these materials, are also able to modulate mucosal immunity of the intestinal tract.<ref>{{cite journal | last = Tsukada | first = C | coauthors = Yokoyama H, Miyaji C, Ishimoto Y, Kawamura H, Abo T | year = 2003 | month = January | title = Immunopotentiation of intraepithelial lymphocytes in the intestine by oral administrations of beta-glucan | journal = Cellular immunology | volume = 221 | issue = 1 | pages = 1-5 | publisher = [[Academic Press]] | location = United States | issn = 0008-8749 | pmid = 12742376 }}</ref> In the central nervous system, β-glucans activate [[microglial cells]].<ref>{{cite journal | last = Muller | first = CD | coauthors = Bocchini V, Giaimis J, Guerrieri P, Lombard Y, Poindron P | year = 1994 | month = May | title = Functional beta-glucan receptor expression by a microglial cell line | journal = Research in immunology | volume = 145 | issue = 4 | pages = 267-275 | publisher = [[Elsevier]] | location = France | issn = 0923-2494 | pmid = 7824804 }}</ref> These cells act as scavengers of the brain cell debris and play a positive role in [[Alzheimer's disease]], [[AIDS]], [[ischemia]] injury and [[multiple sclerosis]].<ref>{{cite journal | last = Haga | first = S | coauthors = Akai K, Ishii T | year = 1989 | title = Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. | journal = Acta neuropathologica | volume = 77 | issue = 6 | pages = 569-575 | publisher = [[Springer Verlag]] | location = Germany | issn = 0001-6322 | pmid = 2750476 }}</ref><ref>{{cite journal | coauthors = Bolcal C, Yildirim V, Doganci S, Sargin M, Aydin A, Eken A, Ozal E, Kuralay E, Demirkilic U, Tatar H | date = [[2007-05-15]] | title = Protective effects of antioxidant medications on limb ischemia reperfusion injury | journal = The Journal of surgical research | volume = 139 | issue = 2 | pages = 274-279 | publisher = [[Academic Press]] | location = United States | issn = 0022-4804 | pmid = 17349658 }}</ref>


==Functions in the Body==
==Functions in the Body==


Beta-1,3 glucans improve the body’s immune system defense against foreign invaders by enhancing the ability of macrophages, neutrophils and natural killer cells to respond to and fight a wide range of challenges such as bacteria, viruses, fungi, and parasites.
Beta-1,3 glucans improve the body’s immune system defense against foreign invaders by enhancing the ability of macrophages, neutrophils and natural killer cells to respond to and fight a wide range of challenges such as bacteria, viruses, fungi, and parasites.


'''Symptoms and Causes of Deficiency:''' Beta-1, 3 glucans do not occur naturally in humans, hence no deficiency condition exists.
'''Symptoms and Causes of Deficiency:''' Beta-1, 3 glucans do not occur naturally in humans, hence no deficiency condition exists.


'''Absorption:''' For best results, Beta 1, 3-D glucan should be taken on an empty stomach. Enterocytes reportedly facilitate the transportation of beta-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.[57] 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.[58] M cells within the Peyer’s Patches physically transport the insoluble whole glucan particles into the GALT.[12]
'''Absorption:''' For best results, Beta 1, 3-D glucan should be taken on an empty stomach. Enterocytes reportedly facilitate the transportation of beta-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.<ref>{{cite journal | coauthors = Frey A, Giannasca KT, Weltzin R, Giannasca PJ, Reggio H, Lencer WI, Neutra MR | date = [[1996-09-01]] | title = Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting | journal = The Journal of experimental medicine | volume = 184 | issue = 3 | pages = 1045-1059 | publisher = [[Rockefeller University Press]] | location = United States | issn = 0022-1007 | pmid = 9064322 }}</ref> 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.<ref>{{cite journal | coauthors = Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, Orita K | year = 1984 | month = June | title = Krestin (PSK) | journal = Cancer treatment reviews | volume = 11 | issue = 2 | pages = 131-155 | publisher = Saunders | location = England | issn = 0305-7372 | pmid = 6238674 }}</ref> M cells within the Peyer’s Patches physically transport the insoluble whole glucan particles into the GALT.<ref name="Hong 04"/>


'''Dietary Sources:''' Although beta-1 3 glucans occur in baker’s yeast, seaweed, grains such as oats and barley, and numerous mushrooms, they are not readily usable in their natural state. The indigestible cell walls of these substances must be processed in order to free up the beta-1, 3 glucans and make them available for useful purposes.
'''Dietary Sources:''' Although beta-1 3 glucans occur in baker’s yeast, seaweed, grains such as oats and barley, and numerous mushrooms, they are not readily usable in their natural state. The indigestible cell walls of these substances must be processed in order to free up the beta-1, 3 glucans and make them available for useful purposes.
Line 115: Line 117:


'''Nutrient/Nutrient Interactions:''' None known
'''Nutrient/Nutrient Interactions:''' None known

==References==

[1] Teas J, “The dietary intake of Laminarin, a brown seaweed, and breast cancer prevention,” Nutr. Cancer 1983; 4(3): 217-22.


[2] Wasser SP, Weis AL, Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective, Crit. Rev. Immunol. 1999; 19(1): 65-96.


[3] Miura NN, Ohno N, Aketagawa J, et al., Blood clearance of (1-->3)-beta-D-glucan in MRL lpr/lpr mice, FEMS Immunol Med Microbiol. 1996 Jan; 13(1): 51- 57.


[4] Chihara G, Recent Progress in immunopharmacology and therapeutic effects of polysaccharides, Dev Biol Stand. 1992; 77:191-7.


[5] DiLuzio N.R. Williams D.L. et al, Comparative evaluation of the tumor inhibitory and antibacterial activity of solubilized and particulate glucan, Recent Results Cancer Res 75:165-172. 1980.


[6] Morikawa K, Takeda R, Yamazaki M, et al., “Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear beta-1, 3-D-glucan and other immunomodulators in murine cells,” Cancer Res. 1985 45(4): 1496-501.


[7] Mansell PW, Ichinose H, Reed RJ, et al., “Macrophage-mediated destruction of human malignant cells in vivo,” J Natl Cancer Inst. 1975 Mar; 54(3): 571-80.


[8] Sveinbjornsson B, Rushfeldt C, Seljelid R, et al., “Inhibition of establishment and growth of mouse liver metastases after treatment with interferon gamma and beta-1, 3-D-glucan,” Hepatology. 1998 May; 27(5): 1241-8.


[9] Thompson IM, Spence CR, Lamm DL, et al., “Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide,” Am J Med Sci. 1987 Nov; 294(5): 294-300.


[10] Wakui A, Kasai M, Konno K, et al., “Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group,” Gan To Kagaku Ryoho. 1986 Apr; 13(4 Pt 1): 1050-9.


[11] Vetvicka, V., Thornton, B. P. and Ross, G. D. 1996. Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J. Clin. Invest. 98:50-61.


[12] Hong, F., Yun, J. Baran J.T., Allendorf, D.J., Hansen, R. D. Ostroff, G.R., Xing, P.X., Cheung, N. V. and Ross, G. D. 2004. Mechanism by which orally administered b-1,3 glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J. Immunol. 173:797-806.


[13] Hong F., Hansen, R. D., Yan, J. Allendorf, D. J., Baran, J. T., Ostroff, G. R. and Ross G. D. 2005. Beta-glucan functions as an adjuvant for monoclonal immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res. 63:9023-9031.


[14] Thornton B. P., Vetvicka, V., Pitman, M., Goldman, R. C. and Ross G. D. 1996. Analysis of the sugar specificity and molecular location of the beta- glucan-binding site of complement receptor type 3 (CD11b/CD18). J.Immunol. 156:1235-1246.


[15] Gelderman, K. A., Tomlinson, S., Ross, G. D., and Gorter, A. 2004. Complement function in mAb-mediated cancer immunotherapy. Trends in Immunol. 25:158-164


[16] Vetvicka, V., Terayma, K., Mandeville, R., Brousseau, P., Kournakakis, B. and Ostroff, G. 2002. Pilot study: Orally-administered yeast beta 1-3- glucan prophylactically protects against anthrax infection and cancer in mice. JANA 5:1-5.


[17] Fujimoto, S. 1989. Clinical efficacies of schizophyllan (SPG) on advanced gastric cancer. Nippon Geka Gakkai Zasshi, 90:1447-1450.


[18] Hanaue, H., Tokuda, Y., Machimura, T., Kamijoh, A., Kondo, Y., Ogoshi, K., Makuuchi, H., Nakasaki, H., Tajima, T., and Mitomi, T. 1989. Effects of oral lentinan on T-cell subsets in peripheral venous blood. Clin. Ther. 11:614-622.


[19] Rice, P.J., Adams, E.L., Ozmet-Skelton, T., Gonzales, A.J., Goldman, M.P., Lockhart, B.E., Barker, L.A., Bruel, K.F., dePonti, W.K., Kalbfleisch, J.H., Ensley, H.E., Brown, GB.D., Gordon, S., and Williams, D.L. 2005. Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. J, Pharmacol. Exp. Ther. 314:1079-1086.


[20] Suyuki, I., Hashimoto, K., Ohno, N., Tanaka, H., and Yadomae, T. 1989. Immunomodulation by orally administered beta-glucan in mice. Int. J. Immunopharmacol. 11:761-769.


[21] Demir, G., Klein, H.O., Mandel-Molinas, N., and Tuzuner, N. Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer. Int. Immunopharmacol. 7:113-116.



[22] Babineau, T. J., Marcello, P., Swalis, W., Kenler, A., Bistrian, B., and Forse, R. A. 1994. Randomized phase I/II trial of a macrophage-specific immunomodulatory (PGG-glucan) in high-risk surgical patients. Annals of Surgery 220:601-609.


[23] Babineau, T. J., Hackford, A., Kenler, A., Bistrian, B., Forse, R. A., Fairchild, P. G., Heard, S., Kerovack, M., Caushaj, P., and, P. 1994. A phase II multicenter, double-blinded, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-Glucan) in high-risk surgical patients. Arch. Surg. 129:1204-1210.


[24] Patchen et al. 1999. Effect of PGG-Glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Arch. Surg. 134:977-983


[25] Dellinger, E.P., Babineau, T.J., Bleicher, P., Kaiser, A.B., Seibert, G.B., Postier, R.G., Vogel, S.B., Norman, J., Kaufman, D., Galandiuk,S., Robert, E. 1999. Effect of PGG-Glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Arch. Surg. 134:977-983.


[26] Vetvicka, V., Vetvickova J., 2007. An evaluation of the immunological activities of commercially available β1,3-Glucans. JANA 10:25-31.


[27] Stone,B.A. and Clark,A.E. 1993. Chemistry and Biology of (1-3)-beta-Glucans. Portland Press, Ltd., London


[28] Patchen, M. L. and T. J. MacVittie. 1983. Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan. Immunopharmacology 5:303-313.


[29] Patchen, M. L., N. R. Di Luzio, P. Jacques, and T. J. MacVittie. 1984. Soluble polyglycans enhance recovery from cobalt-60--induced hemopoietic Injury. J. Biol. Response Mod. 3:627-633.


[30] Patchen M. L., T. J. MacVittie, and L. M. Wathen. 1984. Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells. Experientia 40:1240-1244.


[31] Petruczenko, A. 1984. Glucan effect on the survival of mice after radiation exposure. Acta. Physiol.Pol. 35:231-236.


[32] Patchen, M. L. and T. J. MacVittie . 1986. Comparative effects of soluble and particulate glucans on survival in irradiated mice. J. Biol. Response Mod.5:45-60.


[33] Patchen, M. L., T. Vaudrain, H. Correira, T. Martin, and D. Reese. 1998. In vitro and in vivo hematopoietic activities of Betafectin PGG-glucan. Exp. Hematol. 26:1247-1254.


[34] Turnbull, J. L., M. L. Patchen, and D. T. Scadden. 1999. The polysaccharide, PGG-glucan, enhances human myelopoiesis by direct action independent of and additive to early-acting cytokines. Acta Haematol. 102:66-71.


[35] Tomoda M, Ohara N, Shimizu N, and Gonda R. 1994. Characterization of a novel glucan, which exhibits reticuloendothelial system-potentiating and anti-complementary activities, from the rhizome of Cnidium officinale. Chem. Pharm. Bull. 42:630-633.


[36] Vetvicka, V., Dvorak, B., Vetvickova, J., Richter, J., Krizan, J., Sima, P., and Yvin, J.C. 2007. Orally administered (1-3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity. Int. J. Biol. Macromol. 40:291-298.


[37] Mucksova, J., Babicek, K., and Pospisil, M. 2001. Particulate 1,3--D-glucan, carboxymethylglucan and sulfoethylglucan - influence of their oral or intraperitoneal administration on immunological respondence of mice. Fol. Microbiol. 6:559-563.


[38] Allendorf, D. J., Baran, J. T., Ratajczak, M. Z., Dyke, C. W. and G. Ostroff.2003. Oral WGP Beta Glucan Treatment Accelerates Myeloid Recovery after Radiation Exposure. Presented at BTR 2003. March, 2003.


[39] Cramer, D. E., D. J. Allendorf, J. T. Baran, R. Hansen, J. Marroquin, B. Li, J.Ratajczak, M. Z. Ratajczak, and J. Yan. 2006. b-Glucan enhances complement-mediated hematopoietic recovery after bone marrow injury. Blood. 2006;107:835-840.


[40] Onderdonk, A. B., R. L. Cisneros, P. Hinkson and G. Ostroff. 1992. Anti-infective effect of a poly b 1-6-glucotriosyl-b1-3 glucopyranose glucan in vivo. Infection & Immunity 60:1642-1647.


[41] Kernodle, D.S., H. Gates and A. B. Kaiser. 1998. Prophylactic anti-infective activity of poly-[1-6]-b-D-glucopyranosyl-[1-3]-b-D-glucopyranose glucan in a guinea pig model of Staphylococcal wound infection. Antimicrobial Agents Chemotherapy. 42:545-549.


[42] Tzianabos, A.O., F. C. Gibson III, R. L. Cisneros and D. L. Kasper. 1998. Protection against experimental intraabdominal sepsis by two polysaccharide immunomodulators. J. Infect. Dis. 178:200-206.


[43] Sener, G., Toklu, H. Ercan,F., and Erkanh,G. 2005. Protective effect of - glucan against oxidative organ injury in a rat model of sepsis. Int. Immunopharmacol. 5:138701396.


[44] Portera, CA. Love, EJ. Memore, L. Zhang, L. Miller, A. Browder, W. Williams, DL. Effect of macrophage stimulation on collagen biosynthesis in the healing wound. Am Surg. 1997 Feb;63(2):125-31.


[45] Browder, W. Williams, D. Pretus, H. Olivero, G. Enrichens, F. Mao, P. Franchello, A. Beneficial effect of enhanced macrophage function in the trauma patient. Ann Surg. 1990 May;211(5):605-12; discussion 612-3.


[46] Browder, IW. Williams, DL. Kitahama, A. Di Luzio, NR. Modification of post-operative C. albicans sepsis by glucan immunostimulation. Int J Immunopharmacol. 1984;6(10):19-26.


[47] Browder, W. Rakinic, J. McNamee, R. Jones, E. Williams, D. Di Luzio, N. Protective effect of nonspecific immunostimulation in postsplenectomy sepsis. J Surg Res. 1983 Dec;35(6):474-9.


[48] Kirmaz,C., Bayrak, P., Yilmaz, O., and Yuksel, H. 2005. Effects of glucan treatment on the Th1/Th2 balance in patients with allergic rhinitis: a double-blind placebo-controlled study. Eur. Cytokine Netw. 16:128-134.


[49] Kogan, G., Stasko, A., Bauerova, K., Polovka, M., Soltes, L., Brezova, V., Navarova, J., Mihalova, D. 2005. Antioxidant properties of yeast (1-3)--D-glucan studied by electron paramagnetic resonance spectroscopy and its activity in the adjuvant arthritis. Carbohydrate Polymers 61:18-28.


[50] Keogh, G.F., Cooper, G.J.S., Mulvey, T.B., McArdle, B.H., Coles, G.D., Monro, J.A., Poppitt, S.D. 2003. Randomized controlled crossover study of the effect of a highly beta-glucan-enriched barley on cardiovascular disease risk factors in mildly hypercholesterolemic men. Am.J. Clin. Nutr. 79:711-718.


[51] Dongowski, G., Huth, M., Gebhardt, E., Flamme, W. Dietary fiber-rich barley products beneficially affect the intestinal tract of rats. J. Nutr. 2002;132:3704-3714.


[52] Battilana, P., Ornstein, K., Minehira, K., Schwarz, J.M., Acheson, K., Schneiter, P., Burri, J., Jequier, E., Tappy, L. Mechanisms of action of beta-glucan in postprandial glucose metabolism in healthy men. Eur. J. Clin. Nutr. 2001;55:327-333.


[53] Tsukada, C., Yokoyama, H., Miyaji, C., Ishimoto, Y., Kawamura, H., Abo, T. Immunopotentiation of intraepithelial lymphocytes in the intestine by oral administrations of beta-glucan. Cell. Imunol. 2003;221:1-5.


[54] Muller, C.D., Bocchini, V., Giaimis, J., Guerrieri, P., Lombard, Y., Poindron, P. Functional beta-glucan receptor expression by a microglial cell line. Res. Immunol. 1994;145:267-275.


[55] Haga, S., Akai, K., Ishii, T. Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol. 1989;77:569-575.


[56] Bolcal, C., Yildirim, V., Daganci, S., Sargin, M., Aydin, A., Eken, A., Ozal, E., Kuralay, E., Demirkilic, U., Tatar, H. 2007. Protective effects of antioxidant medications on limb ischemia reperfusion injury. J. Surg. Res. 139:274-279.


[57] Frey A; Giannasca KT; Weltzin R, t al., “Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting,” J Exp Med, 1996 Sep 1, 184:3, 1045-59.


[58] Tsukagoshi S, Hashimoto Y, Fujii G, et al., “Krestin (PSK),” Cancer Treat Rev, 1984 Jun, 11:2, 131-55.
rative infections by 39% after high-risk noncolorectal operations.


==Medical applications==
==Medical applications==
Line 366: Line 133:


==References==
==References==
{{reflist|2}}
<references/>


[[Category:Food additives]]
[[Category:Food additives]]

Revision as of 22:40, 7 May 2008

β-Glucans (or beta-glucans) are polysaccharides occurring in the bran of cereal grains, the cell wall of baker's yeast, certain types of fungi, and many kinds of mushrooms. The cereal based beta-glucans occur most abundantly in barley and oats and to a much lesser degree in rye and wheat. They are useful in human nutrition as texturing agents and as soluble fiber supplements, but problematic in brewing as excessive levels make the wort too viscous. An insoluble (1,3/1,6) beta glucan derived from baker's yeast has a different molecular structure than that of its soluble (1,3/1,4) counterparts and has a greater biological activity due to its structural "branching". Yeast derived beta glucans are notable for their immunomodulatory function. The differences between soluble and insoluble beta glucans are significant in regards to application, mode of action, and overall biological activity.

Overview

Glucans are polysaccharides that only contain glucose as structural components. Beta 1,3-D glucans are chains of D-glucose molecules, with the six-sided D-glucose rings connected at the 1 and 3 positions. Smaller side chains branch off the 1,3 polysaccharide “backbone.” The most active form of Beta 1,3-D glucans are apparently those that contain 1,6 side-chains branching off from the longer beta-1,3 glucan backbone. These are referred to as beta-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 beta 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 beta-1,3 glucans exist as double or triple stranded helix chains. In some cases, proteins linked to the beta-1,3 glucan backbone may also be involved in providing therapeutic activity. Although these compounds have exciting potential for enhancement of the immune system, it must be emphasized that this research is in its infancy, and there are differing opinions on which molecular weight, shape, structure, and source of beta-1,3 glucans provide the greatest therapeutic benefit.

One of the most common sources of Beta 1,3-D glucan is derived from the cell wall of baker’s yeast (Saccharomyces cerevisiae). However, beta-1,3 glucans are also extracted from the bran of some grains such as oats and barley. The Beta 1,3-D glucans from yeast are often insoluble whereas those extracted from grains tend to be soluble. Other sources include some types of seaweed,[1] and various species of mushrooms such as Reishi, Shiitake, and Maitake.[2]

Beta 1,3-D glucans are being referred to as biological response modifiers because of their ability to activate the immune system.[3] However, it should be noted that the activity of Beta 1, 3-D glucan is different from agents that stimulate the immune system. Agents that stimulate the immune system can push the system to over-stimulation, and hence are contraindicated in individuals with autoimmune diseases, allergies, or yeast infections. Beta 1, 3-D glucans seem to make the immune system work better without becoming overactive. They accomplish this by activating phagocytes, which are immune system cells whose function is to trap and destroy foreign substances in our bodies such as bacteria, viruses, fungi, and parasites.[4] In addition to enhancing the activity of phagocytes, beta-1,3 glucans also reportedly lower elevated levels of LDL cholesterol, aid in wound healing, help prevent infections, enhance NK cell function, and help in the prevention and treatment of cancer.

Clinical Applications

Cancer

β-Glucan has been used as an immunoadjuvant therapy for cancer since 1980, primarily in Japan. Numerous studies report that beta-1, 3 glucan has anti-tumor and anti-cancer activity.[5][6] In one study, intralesional administration of beta-1,3 glucans resulted in rapid tumor shrinkage.[7] In another study with mice, beta 1,3 glucan in conjunction with interferon gamma inhibited both the establishment of tumors and liver metastasis.[8] In some studies, beta-1,3 glucans enhanced the effects of chemotherapy. In studies on bladder cancer with mice, administration of cyclophosphamide, in conjunction with beta-1,3 glucans derived from yeast resulted in reduced mortality.[9] In human patients with advanced gastric or colorectal cancer, the administration of beta-1,3 glucans derived from shiitake mushrooms, in conjunction with chemotherapy resulted in prolonged survival times compared to a control group receiving identical chemotherapy.[10]

Preclinical studies have shown that a soluble yeast β-glucan product, Imprime PGG, when used in combination with certain monoclonal antibodies or cancer vaccines, offers significant improvements in long-term survival versus monoclonal antibodies alone.[11] This benefit, however, does not result from Betafectin enhancing the specific killing action of the antibody. The anti-tumor activity is caused by a unique killing mechanism that involves neutrophils that are primed with Betafectin and which are not normally involved in the fight against cancer.[11][12] Recent research by Hong et al, demonstrates that this mechanism of action is effective against a broad range of cancers when used in combination with specific monoclonal antibodies that activate or cause complement to be bound to the tumor.[13] The complement enables these primed neutrophils to find and bind to the tumor, which facilitates killing. Innate immune cells are the body’s first line of defense and circulate throughout the body engaging in an immune response against “foreign” challenges (bacteria, fungus, parasites). Typically, neutrophils are not involved in the destruction of cancerous tissue because these immune cells view cancer as "self" rather than foreign or "non-self." Current cancer immunotherapies involve monoclonal antibodies and vaccines, which stimulate the acquired immune response, but do nothing to change the innate immune system's view of cancer as "self." As a result the monoclonal antibodies alone do not engage or initiate the potential killing ability of the innate immune system, which is our primary mechanism of defense against bacteria and yeast (fungal) infections.

Dr. Gordon Ross and Dr. Vaclav Vetvicka, respected immunologists and cancer researchers at the University of Louisville, discovered that a receptor on the surface of these innate immune cells called Complement Receptor 3 ( CR3 or CD11b/CD18) was responsible for binding to fungi or yeast, allowing the immune cells to recognize them as "non-self."Cite error: A <ref> tag is missing the closing </ref> (see the help page). Both of these receptor sites must be simultaneously occupied to trigger the innate immune cell to destroy the yeast or fungi. Two obstacles prevent neutrophils from using this mechanism of action against cancer. First, the body usually does not generate enough natural antibodies to bind to the tumor, and this prevents the activation and attachment of (or “fixing”) complement to the surface of the cancer cell. Therefore, neutrophils don’t bind to cancer via the first receptor site of CR3. The second obstacle is that even when the natural antibody response is supplemented with monoclonal antibodies that fix complement and binding occurs at the first site, tumors do not contain a foreign carbohydrate serving as “second signal” on their surface that allows neutrophils to recognize the cancer as "non-self “.Cite error: A <ref> tag is missing the closing </ref> (see the help page).

Dr. Ross discovered that a bio-processed fragment of Imprime PGG specifically binds to the second CR3 receptor site on neutrophils. When neutrophils bind to tumors, the Betafectin allows them to “see” cancer as if it were a yeast or fungal pathogen and provide the “second signal” to trigger killing. In summary, Betafectin engages neutrophils in the fight against cancer, dramatically and synergistically enhancing the effectiveness of complement activating monoclonal antibodies and vaccines through a different killing mechanism.

Multinational research has successfully demonstrated that the oral form of yeast Beta 1,3-D glucan has similar protective effects as the injected version, including defense against infectious diseases and cancer.[14][15][16][17][18] Recently, orally-delivered glucan was found to significantly increase proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer.[19]

The technology has wide applicability for cancer therapy. Each form of cancerous tumor cell has specific antigens on the cell surface, some of which are common to other types of cancer. (Example: Mucin 1 is present on about 70% of all types of cancer cells) Different immunotherapies target different antigens for binding monoclonal antibodies to tumor cells. This has resulted in the development of hundreds of monoclonal antibodies, many targeting a different specific antigen on cancer cells. In research studies, Betafectin has improved the effectiveness of all complement-activating monoclonal antibodies tested including breast, liver and lung cancer (company data). The magnitude of success varies based on the specific monoclonal antibody used and the type of cancer.

Prevention of infection

To date there have been numerous studies and clinical trials conducted with the soluble yeast β-glucan and the whole glucan particulate. These studies have ranged from the impact of β-glucan on post-surgical nosocomial infections to the role of yeast β-glucans in treating anthrax infections.

Post-surgical infections are a serious challenge following major surgery with estimates of 25-27% infection rates post-surgery.[20] Alpha-Beta Technologies conducted a series of human clinical trials in the 1990’s to evaluate the impact of β-glucan therapy for controlling infections in high-risk surgical patients.[20] In the initial trial 34 patients were randomly (double-blind, placebo-controlled) assigned to treatment or placebo groups. Patients that 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 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 [21] further studied the impact of β-glucan for reducing the incidence of infection with high-risk surgical patients. The authors found a similar result with a dose-response trend (higher dose provided greater reduction in infectious occurrences than low doses). In the human clinical trial 67 patients were randomized and received either a placebo or a dose of 0.1, 0.5, 1.0 or 2.0 mg PGG-Glucan per KG of body weight. Serious infections occurred in four patients that received the placebo, three patients that received the low dose (0.1 mg/KG) of PGG-Glucan and only one infection was observed at 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.[22] 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.

At this point in the development of an injectable form of b-glucan (Betafectin PGG-glucan) most scientists already concluded that yeast-derived b-glucan promoted phagocytosis and subsequent killing of pathogenic bacteria. 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. The results of the phase III human clinical trial showed that injectable PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations.[22]

There have been studies with humans and animal models that further support the efficacy of β-glucan in combating various infectious diseases. One human study demonstrated that consumption of oral whole glucan particles increased the ability of immune cells to consume a bacterial challenge (phagocytosis). The total number of phagocytic cells and the efficiency of phagocytosis in healthy human study participants increased while consuming a commercial particulate yeast β-glucan. This study demonstrated the potential for yeast β-glucan to increase the reaction rate of the immune system to infectious challenges. The study concluded that oral consumption of whole glucan particles represented a good enhancer of natural immunity.

Anthrax is a disease that cannot be tested in human studies for obvious reasons. In a study conducted by the Canadian Department of Defense, Dr. Kournikakis showed that orally administered yeast β-glucan given with or without antibiotics protected mice against anthrax infection.[14] 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. The hopeful inference is that similar results would be observed with humans.

Since there are many commercial products on the market called “glucan”, there is much confusion among consumers as to which type(s) may be the most effective. One of the most comprehensive published studies to date showed Glucan #300, a highly purified yeast glucan, to be “the biologically most relevant immunomodulator” out of a wide ranging group.[23]

Radiation exposure

β-glucan is a well-known biological response modifier (BRM) isolated from the yeast cell wall polysaccharides and is made up entirely of glucose β(1,3)-linked together in linear chains with variable frequency of β(1,6)-linked side chains.[24] 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).[25] Research was carried out initially with particulate β-glucan and later with soluble β-glucans, all of which were administered intravenously to mice.[26][27][28] 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.[29] Other reports showed that β-glucan could reverse the myelo-suppression produced with chemotherapeutic drugs such as fluorouracil,[22] carboplatinum or cyclophosphamide.[30] 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.[20] 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.[31]

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,[12][32][33][34] opening the oral route of administration as a more pleasant alternative. A study by Allendorf et al.[35] 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.[33] 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.[36] or Vetvicka [33] clearly demonstrated that oral β-glucan stimulates hematopoiesis in radiation-treated mice. Currently, there is renewed interest in the potential usefulness of β-glucan as a radioprotective drug for chemotherapy, radiation therapy and nuclear emergencies, particularly because glucan can be used not only as a treatment, but also as a prophylactic.

Septic shock

One of the mechanisms of the immune-enhancing ability of yeast β-glucan is its ability to prime leukocytes to more easily locate and kill non-self cells including bacteria. Early research by Onderdonk et al.[37] 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. Additional research further supports that yeast β-glucan reduces septic shock by killing bacteria present in blood. 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.[38] Research on the use of yeast β-glucan immunomodulators as a means of treating and preventing bacterial sepsis is well documented.[37][38][39] Recent reports on glucan and sepsis revealed another possible mechanism - glucan protects against oxidative organ injury.[40]

Surgery

There have been numerous studies and clinical trials conducted with the soluble yeast β-glucan particle and the whole glucan particle. Immunomodulators that enhance macrophage function have been shown to be beneficial in human, as well as, animal models. One such study that looked at this correlation examined wound tensile strength and collagen biosynthesis. Positive effects were observed.[41]

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%). Further such trials to evaluate Biological Response Modifiers (BRM’s) in trauma patients are indicated.[42]

Yeast derived beta glucan significantly enhanced phagocytic activity in control and operated mice. In an experimental C. albicans model, mice had induced sepsis along with a midline laparotomy. The non-operated mice on glucan had a 100% survival vs. 73% in the surgical group. Detrimental effects of surgery on survival of C. albicans infection manifested in a 47% survival in the non-surgical vs a 20% survival in the surgery-infected group.[43]

The nonspecific immunostimulation of yeast derived glucan appears to have significant potential as a treatment strategy against post-operative infections. In a post splenectomy mouse model, glucan increased survival vs. controls via 75% as opposed to 27%, Severe sepsis enhances risks in both adult and pediatric patients. These works suggest another option beyond prophylactic antibiotics and bacterial vaccines that often have limited success against morbidity and mortality.[44]

Wound healing

Macrophage activity is known to play a key role in wound healing from surgery or trauma. In both animal and human studies, therapy with Beta glucan has provided improvements such as fewer infections, reduced mortality, and stronger tensile strength of scar tissue.

Allergic rhinitis

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. Based on these studies, glucan may have a role as an adjunct to standard treatment in patients with allergic diseases.[44]

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.[45]

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 and cardiovascular disease hazards, is also mediated by b-glucans.[46] It is known that cereals, mushrooms and yeast facilitate bowel motility and can be used in amelioration of intestinal problems, particularly obstipation.[47][48] Non-digestible b-glucans, forming a remarkable portion of these materials, are also able to modulate mucosal immunity of the intestinal tract.[49] In the central nervous system, β-glucans activate microglial cells.[50] These cells act as scavengers of the brain cell debris and play a positive role in Alzheimer's disease, AIDS, ischemia injury and multiple sclerosis.[51][52]

Functions in the Body

Beta-1,3 glucans improve the body’s immune system defense against foreign invaders by enhancing the ability of macrophages, neutrophils and natural killer cells to respond to and fight a wide range of challenges such as bacteria, viruses, fungi, and parasites.

Symptoms and Causes of Deficiency: Beta-1, 3 glucans do not occur naturally in humans, hence no deficiency condition exists.

Absorption: For best results, Beta 1, 3-D glucan should be taken on an empty stomach. Enterocytes reportedly facilitate the transportation of beta-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.[53] 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.[54] M cells within the Peyer’s Patches physically transport the insoluble whole glucan particles into the GALT.[12]

Dietary Sources: Although beta-1 3 glucans occur in baker’s yeast, seaweed, grains such as oats and barley, and numerous mushrooms, they are not readily usable in their natural state. The indigestible cell walls of these substances must be processed in order to free up the beta-1, 3 glucans and make them available for useful purposes.

Yeast Derived Beta Glucan

Yeast Beta 1, 3-D Glucan

These are sometimes seen as synonyms:

β-Glucan | (1,3/1,6)-β-D-glucan | whole glucan particulate | 1,3/1,6 glucan | (1→3,1→6) glucan


Dosage Range: From 40 mg to 3000 mg daily.

Most Common Dosage: Variable, depending upon body weight and whether it is being used for maintenance or an acute condition. As a dietary supplement (maintenance use), the most common dose range has been reported as 40-500 mg per day. When the dosage is reported on a kilogram of body weight basis the dose range is 2-6 mg/kg. If the particulate glucan is being self-administered for an acute condition, a higher dose of 500-3000 mg/day is typically administered.

Active Forms: Immune-enhancing activity has been reported for Beta 1, 3-D glucan with 1,6 glucan side chains, which are derived from yeasts. Many varieties of mushrooms have also been reported that have a Beta-1,3/1,4 glucan linkage, similar to glucans from oats and barley.

Dosage Forms: As a dietary supplement the most common forms are capsules and tablets. Additional uses also include topical creams and injectables.

Toxicities, Cautions, and Contraindications: Beta 1, 3-D glucan has been recognized as GRAS and the FDA has accepted notification of the GRAS affirmation. The specific conditions of manufacture, safety data and product specifications apply only to the Beta 1, 3-D glucan produced by a process as defined in the GRAS dossier and FDA Notification. Although side effects are very rare, occasionally an allergic reaction is reported. All sufficiently purified polysaccharidic immunomodulators distinguish themselves by very low toxicity (e.g., for mouse lentinan has LD50 > 1600 mg/kg).

Potential Interactions:

Drug/Nutrient Interactions: None known

Nutrient/Nutrient Interactions: None known

Medical applications

Beta-glucans found in baker's yeast and certain fungi are thought to have anticancer properties. In Japan, mushroom-derived extracts rich in beta-glucans have been used for over 20 years in intravenous forms and are approved for use as adjuncts to chemotherapy. There are phase III trial in the U.S. using beta-glucans with other cancer drugs. No forms of beta-glucans have been approved by the FDA to treat cancer.

Other beta-glucans, such as beta-D-glucan, can play an important role in the diagnosis of toxic mycosis caused by fungi that contain such compounds, such as Candida and Aspergillus species.

Beta-glucan is also promoted as dietary supplement for weight loss. These claims are not well supported by research although beta-glucan (like other soluble fibers) has some effect on effective glycemic index and insulin response.

Beta-D-glucan

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 species. An assay to detect the presence of (1→3)β-D-glucan in the blood has been produced by Fungitell and is marketed as a means of diagnosing invasive fungal infection in patients.[55][56][57]

One of the limitations of the assay is the presence of fungal contaminants in amoxicillin-clavulanate[58] and piperacillin-tazobactam[59] which may result in false-positive results in those patients receiving these antibiotics.

References

  1. ^ Teas, J (1983). "The dietary intake of Laminarin, a brown seaweed, and breast cancer prevention". Nutrition and cancer. 4 (3). Lawrence Erlbaum Associates: 217–222. ISSN 0163-5581. PMID 6302638.
  2. ^ Wasser, SP (1999). "Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective". Critical reviews in immunology. 19 (1). United States: Begell House: 65–96. ISSN 1040-8401. PMID 9987601. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  3. ^ Miura, NN (1996). "Blood clearance of (1-->3)-beta-D-glucan in MRL lpr/lpr mice". FEMS immunology and medical microbiology. 13 (1). England: Blackwell Publishing: 51–57. ISSN 0928-8244. PMID 8821398. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  4. ^ Chihara, G (1992). "Recent progress in immunopharmacology and therapeutic effects of polysaccharides". Developments in biological standardization. 77. Switzerland: Karger: 191–197. ISSN 0301-5149. PMID 1426662.
  5. ^ DiLuzio, NR (1980). "Comparative evaluation of the tumor inhibitory and antibacterial activity of solubilized and particulate glucan". Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer. 75. Germany: Springer Verlag: 165–172. ISSN 0080-0015. PMID 7232829. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ Morikawa, K (1985). "Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear beta-1,3-D-glucan and other immunomodulators in murine cells". Cancer research. 45 (4). United States: American Association for Cancer Research: 1496–1501. ISSN 0008-5472. PMID 3156669. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  7. ^ Mansell, PW (1975). "Macrophage-mediated destruction of human malignant cells in vivo". Journal of the National Cancer Institute. 54 (3). United States: Oxford University Press: 571–580. ISSN 0027-8874. PMID 1123850. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  8. ^ Sveinbjørnsson, B (1998). "Inhibition of establishment and growth of mouse liver metastases after treatment with interferon gamma and beta-1,3-D-glucan". Hepatology (Baltimore, Md.). 27 (5). United States: Wiley: 1241–1248. ISSN 0270-9139. PMID 9581677. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  9. ^ Thompson, IM (1987). "Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide". The American journal of the medical sciences. 294 (5). United States: Lippincott Williams & Wilkins: 294–300. ISSN 0002-9629. PMID 3425579. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  10. ^ Wakui, A (1986). "Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group". Gan to kagaku ryoho. Cancer & chemotherapy (in Japanese). 13 (4 pt 1). Japan: Gan To Kagaku Ryohosha: 1050–1059. ISSN 0385-0684. PMID 3083785. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  11. ^ a b Vetvicka, V (1996-07-01). "Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells". The Journal of clinical investigation. 98 (1). United States: American Society for Clinical Investigation: 50–61. ISSN 0021-9738. PMID 8690804. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  12. ^ a b c Hong, F (2004-07-15). "Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models". Journal of immunology (Baltimore, Md. : 1950). 173 (2). United States: American Association of Immunologists: 797–806. ISSN 0022-1767. PMID 15240666. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  13. ^ Hong, F (2003-12-15). "Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells". Cancer research. 63 (24). United States: American Association for Cancer Research: 9023–9031. ISSN 0008-5472. PMID 14695221. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  14. ^ a b Vetvicka, V (2002). "Pilot Study: Orally-Administered Yeast β1,3-glucan Prophylactically Protects Against Anthrax Infection and Cancer in Mice" (PDF). Journal of the American Nutraceutical Association. 5 (2). Birmingham, AL : The Association: 5–9. ISSN 1521-4524. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ Fujimoto, S (1989). "Clinical efficacies of schizophyllan (SPG) on advanced gastric cancer". Nippon Geka Gakkai Zasshi (in Japanese). 90 (9). Japan: Nippon Geka Gakkai: 1447–1450. ISSN 0301-4894. PMID 2531270. {{cite journal}}: Unknown parameter |month= ignored (help)
  16. ^ Hanaue, H (1989). "Effects of oral lentinan on T-cell subsets in peripheral venous blood". Clinical therapeutics. 11 (5). United States: Excerpta Medica: 614–622. ISSN 0149-2918. PMID 2529966. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  17. ^ Rice, PJ (2005). "Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge". The Journal of pharmacology and experimental therapeutics. 314 (3). United States: American Society for Pharmacology and Experimental Therapeutics: 1079–1086. ISSN 0022-3565. PMID 15976018. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  18. ^ Suzuki, I (1989). "Immunomodulation by orally administered beta-glucan in mice". >International journal of immunopharmacology. 11 (7). England: Elsevier Science: 761–769. ISSN 0192-0561. PMID 2599714. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ Demir, G (2007). "Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer". International immunopharmacology. 7 (1). Netherlands: Elsevier Science: 113–116. ISSN 1567-5769. PMID 17161824. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  20. ^ a b c Babineau, TJ (1994). "Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients". Annals of surgery. 220 (5). United States: Lippincott Williams & Wilkins: 601–609. ISSN 0003-4932. PMID 7979607. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  21. ^ Babineau, TJ (1994). "A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients". Archives of surgery (Chicago, Ill. : 1960). 129 (11). United States: American Medical Association: 1204–1210. ISSN 0004-0010. PMID 7979954. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  22. ^ a b c Dellinger, EP (1999). "Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group". Archives of surgery (Chicago, Ill. : 1960). 134 (9). United States: American Medical Association: 977–983. ISSN 0004-0010. PMID 10487593. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  23. ^ Vetvicka, V (2007). "An Evaluation of the Immunological Activities of Commercially Available β1, 3-Glucans" (PDF). Journal of the American Nutraceutical Association. 10 (1). Birmingham, AL : The Association: 25–31. ISSN 1521-4524. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ Stone, Bruce A. (1993). Chemistry and Biology of (1→3)-β-Glucans. Victoria, Australia: La Trobe University Press. ISBN 978-1863244091. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  25. ^ Patchen, ML (1983). "Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan". Immunopharmacology. 5 (4). Netherlands: Elsevier/North-Holland: 303–313. ISSN 0162-3109. PMID 6853144. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  26. ^ Patchen, ML (1984). "Soluble polyglycans enhance recovery from cobalt-60--induced hemopoietic injury". Journal of biological response modifiers. 3 (6). United States: Raven Press: 627–633. ISSN 0732-6580. PMID 6512563. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  27. ^ Patchen, ML (1984-11-15). "Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells". Experientia. 40 (11). Switzerland: Birkhäuser Verlag: 1240–1244. ISSN 0014-4754. PMID 6500009. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  28. ^ Petruczenko, A (1984). "Glucan effect on the survival of mice after radiation exposure". Acta physiologica Polonica. 35 (3). Poland: Panstwowy Zaklad Wydawnictw Lekarskich: 231–236. ISSN 0044-6033. PMID 6537716. {{cite journal}}: Unknown parameter |month= ignored (help)
  29. ^ Patchen, ML (1986). "Comparative effects of soluble and particulate glucans on survival in irradiated mice". Journal of biological response modifiers. 5 (1). United States: Raven Press: 45–60. ISSN 0732-6580. PMID 3958754. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  30. ^ Patchen, ML (1998). "In vitro and in vivo hematopoietic activities of Betafectin PGG-glucan". Experimental hematology. 26 (13). Netherlands: Elsevier Science: 1247–1254. ISSN 0301-472X. PMID 9845381. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  31. ^ Turnbull, JL (1999). "The polysaccharide, PGG-glucan, enhances human myelopoiesis by direct action independent of and additive to early-acting cytokines". Acta haematologica. 102 (2). Switzerland: Karger: 66–71. ISSN 0001-5792. PMID 10529508. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  32. ^ Tomoda, M (1994). "Characterization of a novel glucan, which exhibits reticuloendothelial system-potentiating and anti-complementary activities, from the rhizome of Cnidium officinale". Chemical & pharmaceutical bulletin. 42 (3). Japan: Pharmaceutical Society of Japan: 630–633. ISSN 0009-2363. PMID 8004712. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  33. ^ a b c Vetvicka, V (2007-03-10). "Orally administered marine (1-->3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity". International journal of biological macromolecules. 40 (4). England: Butterworth-Heinemann: 291–298. ISSN 0141-8130. PMID 16978690. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  34. ^ Mucksová, J (2001). "Particulate 1,3-beta-D-glucan, carboxymethylglucan and sulfoethylglucan--influence of their oral or intraperitoneal administration on immunological respondence of mice". Folia microbiologica. 46 (6). Czech Republic: Slovak Academy Of Sciences: 559–563. ISSN 0015-5632. PMID 11898349. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  35. ^ Oral WGP Beta Glucan Treatment Accelerates Myeloid Recovery after Radiation Exposure. Presented at BTR 2003
  36. ^ Cramer, DE (2006-01-15). "Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury". Blood. 107 (2). United States: American Society of Hematology: 835–840. ISSN 0006-4971. PMID 16179370. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  37. ^ a b Onderdonk, AB (1992). "Anti-infective effect of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan in vivo". Infection and immunity. 60 (4). United States: American Society for Microbiology: 1642–1647. ISSN 0019-9567. PMID 1548086. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  38. ^ a b Kernodle, DS (1998). "Prophylactic anti-infective activity of poly-[1-6]-beta-D-glucopyranosyl-[1-3]-beta-D-glucopryanose glucan in a guinea pig model of staphylococcal wound infection". Antimicrobial agents and chemotherapy. 42 (3). United States: American Society for Microbiology: 545–549. ISSN 0066-4804. PMID 9517930. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  39. ^ Tzianabos, AO (1998). "Protection against experimental intraabdominal sepsis by two polysaccharide immunomodulators". The Journal of infectious diseases. 178 (1). United States: University of Chicago Press: 200–206. ISSN 0022-1899. PMID 9652441. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  40. ^ Sener, G (2005). "Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis". International immunopharmacology. 5 (9). Netherlands: Elsevier Science: 1387–1396. ISSN 1567-5769. PMID 15953565. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  41. ^ Portera, CA (1997). "Effect of macrophage stimulation on collagen biosynthesis in the healing wound". The American surgeon. 63 (2). United States: Southeastern Surgical Congress: 125–131. ISSN 0003-1348. PMID 9012425. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  42. ^ Browder, W (1990). "Beneficial effect of enhanced macrophage function in the trauma patient". Annals of surgery. 211 (5). United States: Lippincott Williams & Wilkins: 605–612, discussion 612-613. ISSN 0003-4932. PMID 2111126. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  43. ^ Browder, IW (1984). "Modification of post-operative C. albicans sepsis by glucan immunostimulation". International journal of immunopharmacology. 6 (1). England: Elsevier Science: 19–26. ISSN 0192-0561. PMID 6724765. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  44. ^ a b Kirmaz, C (2005). "Effects of glucan treatment on the Th1/Th2 balance in patients with allergic rhinitis: a double-blind placebo-controlled study". European cytokine network. 16 (2). France: John Libbey Eurotext: 128–134. ISSN 1148-5493. PMID 15941684. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  45. ^ Kogan, G (2005-07-04). "Antioxidant properties of yeast (1→3)-β-d-glucan studied by electron paramagnetic resonance spectroscopy and its activity in the adjuvant arthritis". Carbohydrate Polymers. 61 (1). Elsevier: 18–28. doi:10.1016/j.carbpol.2005.02.010. ISSN 0144-8617. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  46. ^ Keogh, GF (2003). "Randomized controlled crossover study of the effect of a highly beta-glucan-enriched barley on cardiovascular disease risk factors in mildly hypercholesterolemic men". The American journal of clinical nutrition. 78 (4). United States: American Society of Clinical Nutrition: 711–718. ISSN 0002-9165. PMID 14522728. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  47. ^ Dongowski, G (2002). "Dietary fiber-rich barley products beneficially affect the intestinal tract of rats". The Journal of nutrition. 132 (12). United States: American Society of Nutritional Sciences: 3704–3714. ISSN 0022-3166. PMID 12468611. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  48. ^ Battilana, P (2001). "Mechanisms of action of beta-glucan in postprandial glucose metabolism in healthy men". European journal of clinical nutrition. 55 (5). England: Nature Publishing Group: 327–333. ISSN 0954-3007. PMID 11378805. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  49. ^ Tsukada, C (2003). "Immunopotentiation of intraepithelial lymphocytes in the intestine by oral administrations of beta-glucan". Cellular immunology. 221 (1). United States: Academic Press: 1–5. ISSN 0008-8749. PMID 12742376. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  50. ^ Muller, CD (1994). "Functional beta-glucan receptor expression by a microglial cell line". Research in immunology. 145 (4). France: Elsevier: 267–275. ISSN 0923-2494. PMID 7824804. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  51. ^ Haga, S (1989). "Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody". Acta neuropathologica. 77 (6). Germany: Springer Verlag: 569–575. ISSN 0001-6322. PMID 2750476. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  52. ^ "Protective effects of antioxidant medications on limb ischemia reperfusion injury". The Journal of surgical research. 139 (2). United States: Academic Press: 274–279. 2007-05-15. ISSN 0022-4804. PMID 17349658. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  53. ^ "Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting". The Journal of experimental medicine. 184 (3). United States: Rockefeller University Press: 1045–1059. 1996-09-01. ISSN 0022-1007. PMID 9064322. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  54. ^ "Krestin (PSK)". Cancer treatment reviews. 11 (2). England: Saunders: 131–155. 1984. ISSN 0305-7372. PMID 6238674. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  55. ^ Obayashi T, Yoshida M, Mori T; et al. (1995). "Plasma (13)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes". Lancet. 345: 17–20. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  56. ^ Ostrosky-Zeichner L, Alexander BD, Kett DH; et al. (2005). "Multicenter clinical evaluation of the (1→3)β-D-glucan assay as an aid to diagnosis of fungal infections in humans". Clin Infect Dis. 41: 654–659. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  57. ^ Odabasi Z, Mattiuzzi G, Estey E; et al. (2004). "Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome". Clin Infect Dis. 39: 199–205. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  58. ^ Mennink-Kersten MASH, Warris A, Verweij PE (2006). "1,3-β-D-Glucan in patients receiving intravenous amoxicillin–clavulanic acid". 354 (26): 2834–2835. {{cite journal}}: Cite journal requires |journal= (help); line feed character in |author= at position 22 (help)CS1 maint: multiple names: authors list (link)
  59. ^ Sulahian A, Touratier S, Ribaud P (2003). "False positive test for aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam". N Engl J Med. 349: 2366–2367.{{cite journal}}: CS1 maint: multiple names: authors list (link)