Beta Glucan

Beta glucan is a polysaccharide, an all natural soluble fibrous sugar molecules derived from cell walls of yeast, oats, barley, and certain kinds of mushrooms. These polysaccharides help support the body in a lot of ways due to their efficient ability to fight infections and accelerate healing. It greatly improves general immune responses, as a lot of health researchers consider beta glucan as among the most effective immune health improving substance to date.

Beta glucan is likewise can be found in other grains, bacteria cell walls, seaweeds, and fungi cell walls. Predominantly yeast and mushroom are the two foremost fungal form sources of beta glucan and the key source of materials for all medical researches, literatures, and studies. However, studies have shown that the determining factor on its immune support characteristics is based upon what the product it is isolated from (yeast, mushrooms, etc…).

Research for beta glucan started a few decades back. In the 1940’s, a research scientist named Dr. Louis Pillemer yielded a substance called Zymosan that specifically had an immune activating properties and further research to Zymosan led to the identification of the substance Beta-1, 3-D glucan, as the active ingredient glucan was isolated from the cell walls of Baker’s yeast. Later studies showed it activated immune response [i],[ii] despite the type of attacking invader whether a bacteria[iii],[iv] viruses[v],[vi] fungi[vii], parasites[viii], or tumors[ix],[x],[xi]. From there further researches and studies were conducted that led to what is known today as beta glucan.

Properly derived from a natural food source it can be utilized as a dietary supplement. It keeps the macrophages, i.e. white blood cells, properly balanced and in a constant state of readiness in order for the immune system to respond to any perceived threat. The macrophage is the primary ‘non-specific’ defense mechanisms of our body and its main focus is to located and identify ‘self’ from ‘non-self’ by attacking and destroying the ‘non-self’ invaders by engulfing it and breaking it down. This process is called phagocytosis. In this process of destroying the invaders, anti-bodies are produced by the macrophage which intern help create the immune specific response in order to completely defeat the invader. By having the macrophages in a constant state of readiness a cascading effect occurs, all other immune responses are faster and more effective, including the specific response.

Many researchers consider it to be one of the most effective immune enhancing substances ever discovered. A search conducted through the National Library of Medicine on Beta Glucan produces over 8000 peer-reviewed results. While this is a very large number, detailed studies show there are around 800+ direct studies on Beta Glucan. The Bakers yeast isolate (Saccharomyces cerevisiae), a food source, if properly extracted has been shown to be completely safe and non-toxic. Bakers yeast, and their extracts, have been given a GRAS rating. This is one of the highest, if not the highest safety rating a substance can achieve. The specifications for this rating can be found in 21CFR184.1983 — Sec. 184.1983.

Beta glucan is also known as a biological defense modifier, as they efficiently activate B-cells, T-cells, and macrophage immune cells to effectively support and enhance the immune system and to help fight off infections, viruses, and any other invaders. Its anti-tumor properties can help support to healing people suffering from cancer. Beta glucan specifically helps kill bacteria in the blood, as it has been shown to support lower cholesterol level, help maintain a healthy heart, helps AIDS and HIV patients, burns or radiation exposure, chronic fatigue syndrome, and any other immune system health issues. Beta glucan also help support diabetics manage their blood pressure and glucose levels by delaying gastric emptying.

ABDOMINAL OR THORACIC SURGERY – HARVARD MEDICAL SCHOOL (USA) “There were no adverse drug experiences….is safe and appears to be effective in the further reduction of the morbidity and cost of major surgery.”[xii]

BACTERIAL INFECTIONS – UNIVERSITY OF TROMSO, Norway;  “These studies indicate that glucan confers an enhanced state of host defense against bacterial infections.”[xiii].

CANCER, LUNG AND BREAST – NATIONAL CANCER INST (USA); “The initial 9 patients studied had malignant melanoma, adenosquamous carcinoma of the lung, or carcinoma of the breast. Control and experimental lesions were injected: subsequently biopsies were performed at varying intervals for histologic evaluation. Always when glucan or glucan and RF fraction were administered intralesionally, the size of the lesion was strikingly reduced in as short a period as 5 days. This reduction was associated with necrosis of the tumor and a monocytic infiltrate. In small lesions, resolution was complete, whereas in large lesions, resolution was partial[xiv].

CANCER – MAYO CLINIC (USA); “….. beta-glucan interacts with vitronectin and stimulates tumor necrosis factor alpha release from macrophage’s.”[xv].

CANCER – CHEM PHARM BULL (Japan); “Antitumor and immunomodulating activities of a beta-glucan….”[xvi].

CANCER – UNIVERSITY OF TROMSO (Norway); “Macrophages stimulated by an insoluble beta 1-3-D-glucan from yeast cell walls were able to destroy tumor cells as measured by the release of radioactive label from prelabelled 14C-thymidine cells. Target cells were B-16 melanoma, P-815 mastocytoma, and the L-929 cell line. A significant target cell killing by macrophages stimulated by glucan was observed after 72-96 h.” [xvii].

CANDIDA ALBICANS – DEPARTMENT OF SURGERY, TULANE UNIVERSITY; “Protection against C. albicans was observed in the glucan-treated groups. …These observations suggest that Biologic Response Modifiers such as glucan may be effectively employed in patients who are at risk for post-operative infections.”[xviii].

CHOLESTEROL (LDL) – OTTAWA CIVIC HOSPITAL (Canada); ” The main component of the soluble fiber of oats, beta-glucan, significantly reduced the total and LDL cholesterol levels of hypercholesterolemic adults without changing HDL cholesterol.”[xix].

CHOLESTEROL – DEPARTMENT OF AGRICULTURE (USA); “Beneficial reduction of cholesterol was obtained with modest amounts…..”[xx].

DIABETES – OTTAWA CIVIC HOSPITAL (Canada); “A diet rich in beta-glucan may therefore be of benefit in the regulation of plasma glucose levels in subjects with Type 2 diabetes.”[xxi].

DIABETES – NESTLE RESEARCH CENTER (Switzerland); “Diabetic individuals can benefit from diets that are high in beta-glucan…”[xxii].

COLI, STAPHYLOCOCCUS – DEPARTMENT OF PATHOLOGY, BRIGHAM AND WOMEN’S HOSPITAL (USA, Mass); “Mice challenged with Escherichia coli or Staphylococcus aureus were protected against lethal peritonitis by the intravenous administration of 10 micrograms of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose (PGG) glucan per animal 4 to 6 h prior to bacterial challenge.”[xxiii].

FUNGAL INFECTION – TULANE UNIVERSITY; “The broad spectrum of immunopharmacological activities of glucan includes not only the modification of certain bacterial, fungal, viral and parasitic infections, but also inhibition of tumor growth.”[xxiv].

HEPATITIS, VIRAL – SCIENCE (1980);”Thus glucan is capable of increasing survival, inhibiting hepatic necrosis, and maintaining an activated state of phagocytic activity in mice challenged with [mouse hepatitis virus strain] MHV-A59.”[xxv].

HERPES SIMPLEX 1 – PLANTA MED;  “The antiviral effect of scleroglucan seems to be related to its binding with membrane glycoproteins of HSV-1 particles which impedes the complex interactions of the virus with the cell plasma membrane.”[xxvi].

HIGH RISK SURGICAL PATIENTS – DEPT PHARMACEUTICAL CHEMISTRY , B.I.S. COLLEGE OF PHARMACY, GAGRA INDIA. “…significantly fewer infectious complications than the placebo group (1.4 infections per infected patient for the 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 (ICU) for patients receiving PGG-glucan versus patients receiving placebo.[xxvii].

INFECTION PREVENTION – GYNECOLOGY & OBSTETRICS; “The incidence of hospital pneumonia of 55% and sepsis of 35% confirms results of previous studies of patients with multitrauma. Glucan decreased pneumonia and sepsis to a significantly lower level of 9.5%….The mortality rate related to infection decreased from 30.0 to 4.8%. The lower number of instanceNo problem We s of pneumonia and sepsis….decreased the period of time in the intensive care and the hospital, with a global reduction of 40% on hospital cost.”[xxviii].

INTERLEUKIN – INT J IMMUNOPHARMACOL; “The study demonstrates that; (1) glucan will enhance IL-1 and IL-2 production and (2) elevations in lymphokine production can be maintained up to 12 days post-glucan”[xxix].

PARASITES – TULANE UNIVERSITY (USA); “Trypanosoma cruzi, the causative agent of Chagas’ disease, infects humans and animals….. Glucan significantly (P less than 0.05) increased survival rate as denoted by 60%….”[xxx].

PNEUMONIA – HOSPITAL ARTHUR RIBEIRO DE SABOYA (Brazil); “The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan….”[xxxi].

PROSTATE CANCER; “A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer”[xxxii]

RADIATION SURVIVABILITY– ARMED FORCES RADIOBIOLOGY RESEARCH INSTITUTE (USA); “Immunomodulators, either microbial agents (e.g. glucan, TDM) or recombinant cytokines (e.g. Interleukin-1, colony-stimulating factor), can enhance hematopoietic and functional cell recovery after irradiation.”[xxxiii].

RADIATION – RADIOPROTECTIVE EFFECT; “These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger.”[xxxiv].

RADIATION SURVIVABILITY; Abstract: “Glucan, a beta-1, 3 polyglucose, was administered to mice either 1h before or 1h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistently exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.”[xxxv].

STAPHYLOCOCCAL; “Comparative tumor-inhibotory and anti-bacterial activity of soluble and particulate glucan,” “…these studies demonstrate that a soluble glucan preparation exhibits significant anti-tumor and anti-staphylococcal activity.”[xxxvi].

STAPHYLOCOCCAL; “Mice challenged with Escherichia coli or Staphylococcus aureus were protected against lethal peritonitis by the intravenous administration of 10 micrograms of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose (PGG) glucan per animal 4 to 6 h prior to bacterial challenge.”[xxxvii]

STRESS, PHYSICAL, OR EMOTIONAL – TOWNSEND LETTER FOR DOCTORS, (1996);”The following list includes benefits from the use of Beta 1,3-glucan supplementation: Professional and amateur athletes as well as people who work outdoors intensively. People under physical or emotional stress”[xxxviii].

STRESS; “The significant role of glucans in cancer treatment, infection immunity, stress reduction and restoration of damaged bone marrow has already been established.”[xxxix].

TRAUMA PATIENTS – TULANE UNIVERSITY (USA); “total mortality rate was significantly less in the glucan group (0% versus 29%) (p less then 0.05), the mortality rate from sepsis was not statistically different (0% versus 17.6%). Glucan therapy significantly decreased septic morbidity (9.5% versus 49%; p less than 0.05). Serum IL-1 had a greater increase in glucan patients on day 3 after trauma (143.4 +/- 19.3% versus 78.6 +/- 11.7%; p less than 0.05),…”[xl].

VIRAL DISEASES; “…Beta-glucans have studied for their hypocholesterolemic effects; these mechanisms include: reducing the intestinal absorption of cholesterol and bile acids by binding to glucans; shifting the liver from cholesterol syntheses to bile acid production; and fermentation by intestinal bacteria to short-chain fatty acids, which are absorbed and inhibit hepatic cholesterol syntheses. …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. …there is renewed interest in the potential usefulness of beta-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 [taken in advance for protection].”[xli].

VIRAL INFECTION; “The use of soluble and insoluble beta glucans alone or as vaccine adjuvants for viral and bacterial antigens has been shown in animal models to markedly increase resistance to a variety of bacterial, fungal, protozoan and viral infections.”[xlii].

WOUND HEALING – EAST TENNESSEE STATE UNIVERSITY (USA); “These data indicate that macrophage modulation with glucan phosphate will increase tensile strength in experimental colon and skin wounds. These are just a few of the many studies on Beta Glucan, further, these studies do not reflect the results of any one product, or product line(s) shown to contain Beta Glucan. Also, the delivery methods of the Beta Glucan to the test subjects may have been of different types, two of which are oral and intravenous delivery[xliii] [43].

WOUND HEALING; “Of all the substances tested, glucan was the only substance to exhibit a particularly marked enhancement of the proliferative phase of wound healing.  It appears, from these experiments, that the effect observed by others in terms of the activation of reticuloendothelial [immune response] function by glucan and the activation of macrophages, both locally and systematically, also apply to activation of macrophages in healing wounds.”[xliv].

WOUND HEALING; “The pharmacological capabilities of 1,3-B-glucans include the impartation of tumor inhibition, resistance to infectious disease, and improvements in wound healing.”[xlv].

[i] Heike Stier, Veronika Ebbeskotte and Joerg Gruenwald: Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan, Nutr J. 2014; 13: 38.

[ii] Vaclav Vetvicka and Jana Vetvickova: Glucan supplementation enhances the immune response against an influenza challenge in mice. Ann Transl Med. 2015 Feb; 3(2): 22.

[iii] Hyung Sook Kim, Jin Tae Hong, Youngsoo Kim, and Sang-Bae Han: Stimulatory Effect of β-glucans on Immune Cells, Immune Netw. 2011 Aug; 11(4): 191–195.

[iv] Rice PJ, Adams EL, Ozment-Skelton T, Gonzalez AJ, Goldman MP, Lockhart BE, Barker LA, Breuel KF, Deponti WK, Kalbfleisch JH, et al: Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. The Journal of pharmacology and experimental therapeutics. 2005;314:1079–1086. doi: 10.1124/jpet.105.085415.

[v] Sandeep Rahar, Gaurav Swami, Navneet Nagpal, Manisha A. Nagpal, and Gagan Shah Singh: Preparation, characterization, and biological properties of β-glucans. J Adv Pharm Technol Res. 2011 Apr-Jun; 2(2): 94–103.

[vi] Maurizio Mazzei, et al: Effect of 1,3-1,6 β-Glucan on Natural and Experimental Deformed Wing Virus Infection in Newly Emerged Honeybees (Apis mellifera ligustica), PLoS One. 2016; 11(11): e0166297.

[vii] Sainkhuu Batbayar, Dong Hee Lee and Ha Won Kim: Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1, Biomol Ther (Seoul). 2012 Sep; 20(5): 433–445.

[viii] Rondanelli M1, Opizzi A, Monteferrario F: The biological activity of beta-glucans.Minerva Med. 2009 Jun;100(3):237-45.

[ix] Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E: Effects of beta-glucans on the immune system. Medicina (Kaunas). 2007;43(8):597-606.

[x] Yoon TJ, Koppula S, Lee KH: The effects of β-glucans on cancer metastasis. Anticancer Agents Med Chem. 2013 Jun;13(5):699-708.

[xi] Khawaja Muhammad Imran Bashir and Jae-Suk Choi: Clinical and Physiological Perspectives of β-Glucans: The Past, Present, and Future, Int J Mol Sci. 2017 Sep; 18(9): 1906.

[xii] Babineau TJ, Marcello P, Swails W, Kenler A, Bistrian B, Forse RA: Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients. Ann Surg. 1994 Nov;220(5):601-9.

[xiii] Rasmussen, LT and Seljelid, R: “Novel Immunomodulators With Pronounced In Vitro Effects Caused by Stimulation of Cytokine Release”, Journal of Cellular Biochemistry; 46:60-68. 1991.

[xiv] Mansell P.W.A., Ichinose H., Reed R.J., Krements E.T., McNamee R.B., Di Luzio N.R: “Macrophage-mediated Destruction of Human Malignant Cells in Vitro”. Journal of National Cancer Institute; 54: 571-580. 1975.

[xv] Olson E.J., Standing J.E, et al: “Fungal beta-glucan interacts with vitronectin and stimulates tumor necrosis factor alpha release from macrophages,” Infect Immun 64: 3548-3554. 1996.

[xvi] Kasai, S., Fujimoto S., Nitta K., Baba H., Kunimoto T: “Antitumor activity of polymorphonuclear leukocytes activated by a B-1, 3-D-glucan”. J. Pharmacobiodyn. 14:519-525. Medline.

[xvii] Bogwald J, Johnson E, Seljelid R: The Cytotoxic Effect of Mouse Macrophages Stimulated in vitro by a beta. 1,3-D-Glucan from Yeast Cell Walls. Scand. J. Immuol. 15: 297-304. 1982. Institute of Med Bio, U of Tromso, Norway.

[xviii] Browder W., et al: modification of Post-Operative C. albicans Sepsis by Glucan Immunostimulation, Int. J. Immunopharmac.; 6:19-26. 1984. Dept of Surg and Physiol, Tulane U Sch of Med, LA

[xix] Braaten JT, Wood PJ, Scott FW, Wolynetz MS, Lowe MK, Bradley-White P, Collins MW: Oat beta-glucan reduces blood cholesterol concentration in hypercholesterolemic subjects. Eur J Clin Nutr. 1994 Jul;48(7):465-74.

[xx] Behall KM, Scholfield DJ, Hallfrisch J: Effect of beta-glucan level in oat fiber extracts on blood lipids in men and women. J Am Coll Nutr. 1997 Feb;16(1):46-51.

[xxi] Braaten JT, Scott FW, Wood PJ, Riedel KD, Wolynetz MS, Brulé D, Collins MW: High beta-glucan oat bran and oat gum reduce postprandial blood glucose and insulin in subjects with and without type 2 diabetes. Diabet Med. 1994 Apr;11(3):312-8.

[xxii] Würsch P1, Pi-Sunyer FX: The role of viscous soluble fiber in the metabolic control of diabetes. A review with special emphasis on cereals rich in beta-glucan. Diabetes Care. 1997 Nov;20(11):1774-80.

[xxiii] Onderdonk, A.B., et al: Anti-Infective Effect of Poly-.beta.1-6 -Glucotrisyl-.beta.1-3-Glucopyranose Glucan In Vivo, Infec. Immun.; 60:1642-1647.

[xxiv]DiLuzio N.R: Immunopharmacology of glucan: a broad spectrum enhancer of host defense mechanisms, Trends in Pharmacol. SCI., 4:344-347. Dept of Physiology

[xxv] Williams D.L. and DiLuzio N.R: “Glucan-Induced Modification of murine Viral Hepatitis.  Science (1980), 208: 67-69. 1980.

[xxvi] Marchetti M, Pisani S, Pietropaolo V, Seganti L, Nicoletti R, Degener A, Orsi N: Antiviral effect of a polysaccharide from Schlerotium glucanicum towards herpes simples virus type 1 infection. Planta Med, 62:4, 301-7. Aug 1996.

[xxvii] Sandeep Rahar, Gaurav Swami, Navneet Nagpal, Manisha A. Nagpal, and Gagan Shah Singh: Preparation, characterization, and biological properties of β-glucans, J Adv Pharm Technol Res. 2011 Apr-Jun; 2(2): 94–103.

[xxviii] Maurici da Rocha e Silva et al: Infection Prevention in Patients with Severe Multiple Trauma with the Immunomodulater Beta 1-3 Polyglucose (glucan);” Surgery, Gynecology & Obstetrics; 177:383-388. 1993.

[xxix] Sherwood. E.R., et al: Enhancement of Interleukin-1 and Interleukin-2 Production by Soluble Glucan,” International  Journal of Immunopharmacology.; 9:(3):261-267. 1987.

[xxx] Williams, David & G. Yaeger, Robert & A. Pretus, Henry & Browder, I.William & B. McNamee, Rose & L. Jones, Ernest: Immunization against Trypanosoma cruzi: Adjuvant effect of glucan. International journal of immunopharmacology. 11. 403-10. 10.1016/0192-0561(89)90087-8.

[xxxi] Maurici da Rocha e Silva et al: infection Prevention in Patients with Severe Multiple Trauma with the Immunomodulater Beta 1-3 Polyglucose (glucan); Surgery, Gynecology & Obstetrics; 177:383-388.

[xxxii] Fullerton SA, Samadi AA, Tortorelis DG, Choudhury MS, Mallouh C, Tazaki H, Konno S:  Induction of apoptosis in human prostatic cancer cells with beta-glucan,  Source: Department of Urology, New York Medical College, Valhalla, New York 10595, USA.

[xxxiii] Walker RI: Requirements of radioprotectors for military and emergency needs.Pharmacol Ther. 1988;39(1-3):13-20.

[xxxiv] Patchen M.L., D’Alesandro M.M., Brook I., Blakely W.F. McVittie T.J: “Glucan: Mechanisms Involved in Its ‘Radioprotective’ Effect”. J Leuc Biol.; 42:95-105. 1987.

[xxxv] Patchen ML, MacVittie TJ, Wathen LM: Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells. Experientia. 1984 Nov 15;40(11):1240-4.

[xxxvi] Di Luzio NR, Williams DL, McNamee RB, Edwads BF, Kitahama A: Comparative tumor inhibitory and anti-bacterial activity of soluble and particlate glucan. Int J Cancer. 1979;24:773–779.

[xxxvii] Onderdonk, A.B., et al: “Anti-Infective Effect of Poly-.beta.1-6 -Glucotrisyl-.beta.1-3-Glucopyranose Glucan In Vivo,” Infec. Immun.; 60:1642-1647. 1992.  Dept of Pathology, Channing Lab, Brigham and Women’s Hospital, Boston, MA.

[xxxviii] TOWNSEND LETTER FOR DOCTORS, June (1996)

[xxxix] Vetvicka V: “Glucan-immunostimulant, adjuvant, potential drug,” World J Clin Oncol, 2(2):115-119 Feb 10 2010.

[xl] Browder W1, 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.

[xli] Rondanelli M1, Opizzi A, Monteferrario F: The biological activity of beta-glucans., Minerva Med. 2009 Jun;100(3):237-45.

[xlii] Jamas S, Easson D, Ostroff G: Underivatilized aqueous soluble beta (1,3) glucan, composition and method of making same., U.S. Patent Application 20020032170, March 14, 2002.

[xliii] Portera CA, Love EJ, Memore L, Zhang L, Muller A, Browder W, Williams DL; “Effect of macrophage stimulation on collagen biosynthesis in the healing wound,” Am Surg, 63:2,125-131. Feb 1997.

[xliv] Leibovich S.J., et al: Promotion of Wound Repair in Mice by Application of Glucan”.  J. Reticuloendothel, Soc. 27: 1-11. 1980.

[xlv] Lehtovaara BC, Gu FX; “Pharmacological, Structural, and Drug Delivery Properties and Applications of 1,3-B-Glucans,” Dept of Chem Eng, U of Waterloo, Ontario, Canada; J Agric Food Chem, Jun 7 2011.  PMID 21609131