Beta Glucan Research – Saccharomyces cerevisiae

Beta Glucan Derived from Yeast Cell Wall – Beta 1,3/1,6 glucan and Derivatives

Condition, Function and Disease Indexed References

“I” through “P”

I

“IL-1” through “Pulmonary” (including “Immune Response”, “Infection”, “Inflammation”, “Microparticulate”, “Obesity”, “Particle Size,” “Pneumonia” and “Probiotic” )

IBD – Inflammatory Bowel Disease and IBS – Irritable Bowel Syndrome:

IBD – Inflammatory Bowel Disease-Human Study: Mall John-Peter, Casado-Bedmar M, et al, “A B-Glucan -Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients with Crohn’s Disease and Control Subjects,’ Inflammatory Bowel Diseases, Vol 24, Issue 1 pp 166-178, PMID 29272475, Jan 1, 2018: Quote: “B-Glucan significantly attenuated [weakened] MC-induced paracellular hyperpermeability in CD [Crohn’s Disease] and controls. …We demonstrated beneficial effects of B-glucan on intestinal barrier function and increased B-glucan-passage through FAE model.” Note: mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villlus epithelium (VE) of patients with Crohn’s disease (CD). B-Glucan used was yeast derived Beta 1,3/1,6 glucan.

IBD – Inflammatory Bowel Disease): Spagnuoto R, Cosco C et al, “Beta-glucan, inositol and digestive enzymes improve quality of life of patients with inflammatory bowel disease and irritable bowel syndrome.” Eur Rev Med Pharmacol Sci, Supply:102-107, PMID: 28724171, June 21, 2017. Quote: “We have shown that supplementation with a mixture of beta-glucan, inositol and digestive enzymes reduces bloating, flatulence and abdominal pain, improving the overall clinical condition of IBD-IBS patients.”

IBD: Raa J, “Immune modulation by non-digestible and non-absorbable beta-1,3/1,6-glucan,” Micro Edo in Heal & Disease, Vol 26:1, Issue s3, https://doi.org/103402/mehd.v25.27824, May 29 2015. Quote: “More than 30 years ago, Seljelid and co-workers screened a large number of glucans and glycans …for their macrophage-activating ability in vitro, and found that a particulate beta-1,3/1,6-glucan prepared from baker’s yeast was the most active. …Due to their ability to enhance infection defense mechanisms and simultaneously down-regulate inflammations, beta-1,3/1,6-glucan is very promising as an alternative to the mainstream use of immunosuppressive drugs to treat inflammatory diseases, for instance, IBD. Note: glycans are polysaccharides containing other sugars than glucose.

IBS – Irritable Bowel Syndrome: Ciacci C, Franceschi F, et al, “Effect of beta-glucan, inositol and digestive enzymes in GI symptoms of patients with IBS,” Eur Rev Med Pharmacol Sci, PMID 21796867, WMD, Jun 15, 2011, Quote: “Biointol [a mixture of beta-glucan, inositol and digestive enzymes] administration has shown to improve some IBS symptoms, such as bloating, flatulence and abdominal pain, all connected to the presence of gas inside the intestinal lumen.”

IL-1B, Micronization-Nanoparticle – Carrier Composite (Doxorubicin): Huang J, Wu C, et al, “Chiral Active B-Glucan Nanoparticles for Synergistic Delivery of Doxorubicin and Immune Potentiation,” Int J Nanomedicine, 15-5083-5095, PMID: 32764938, https://doi.org/10.2147/UN.525814-5, Jul 14 2020. Quote: “B-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified. ….B-glucan nonoparticles can activate macrophages to produce immune enhancing cytokines (IL-1B, IL-6, TNF-alpha, IFN-y). This work demonstrates that B-glucans nanoparticles with special chiral feature which leading to strong immunopotentiation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer treatment.”

IL 1 and TNF Alpha Production: Hunter KW, Jr. Berner MD, Sura ME Alvea BN, “IFN-gamma primes macrophages for enhanced TNF-alpha expression in response to stimulatory and non-stimulatory amounts of microparticulate beta-glucan.,”Immunol Lett ; 15:98(1): 115-22.Department of Microbiology and Immunology, University of Nevada School of Medicine, Applied Research Facility, MS-199, Reno, NV 89557, USA. April 2005, Quote: …“we have tested a new microparticulate form of beta-(1–> 3)-D-glucan (MG) from Saccharomyces cerevisiae for its ability to induce proinflammatory cytokine secretion in mouse peritoneal macrophages in vitro, and we have examined the effect of IFN-gamma. MG was rapidly phagocytized by peritoneal macrophages, and these MG-treated macrophages upregulated TNF-alpha, IL-6, and IL-1beta mRNAs and secreted these proinflammatory cytokines. These data suggest that a synergy between IFN-gamma and beta-glucan may have evolved to lower the threshold of sensitivity of the innate immune response to fungal pathogens.” [respond faster in attacking fungal pathogens – mycotoxins]

IL 1 and TNF-µ Production : Hunter K, Washburn R, “Efficacy of topical antimicrobial acid and immunostimulatory B-Glucan in Animal Models of Cutaneous Infection,” U Nevada Medical School-Applied Res Grant, Aug 1998. Quote: “Our laboratory has developed preliminary evidence that B-1,3/1,6 glucans possesses immunostimulatory activity for macrophages in vitro, leading to secretion of the Th-1 cytokines IL-1 B, IL-12, and TNF-µ.”

IL-1 Enhancement: Poutsiaka D.D., et al, “Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production,” Blood 82: 3695-3700 ; Dept of Med, New England Med Ctr, Boston, MA. 1993. Quote: “Because of their differential effects on cytokine production, beta-glucans may be used to therapeutic advantage in the diseases in which IL-1 is implicated.”*

IL 1 Enhancement: Rasmussen LT, Seljelid R,”Introoduction of prostaglandin E2 and interleukin 1 by mouse peritoneal macrophages stimulated with beta-1,3-D-glucan derivatized plastic beads,” Scand J Immunol 26(6): 731-736. Dec 1987.*

Immune (Immunological) modulatory effects: Stier H, Ebbeskotte V, Gruenwald J, “Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan,” Nutr J, 13:38,PMID: 24774968; PMC40112169, Apr 28, 2014. Quote: “The results of all studies [in vivo, in vitro, human clinical trials with dietary insoluble yeast beta-glucans] taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect. …Insoluble B-glucans are able to activate both the innate and adaptive immune responses…Two independent randomized, double-blind, placebo-controlled clinical trials showed that daily oral administration of the proprietary insoluble (1,3)-1,6)-B-glucan, derived from brewers’ yeast, reduced the incidence of common cold episodes during the cold season in otherwise healthy subjects.”

Immune Cell Receptor – Dectin-1: Takano T, Motozono C, et al, “Dectin-1 Intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity,” JBC Papers in Press, Manuscrit M117.800847, Aug 28, 2017. Quote:“Dectin-1 is a well-characterized CLR [c-type lectin receptor] that recognizes B-glucan. …Our bodies are continuously exposed to and infected by various types of pathogens, most of which are recognized by pattern recognition receptors (PRRs)… An…additional member of emerging PRRs is the C-type lectin receptors (CLRs) [including Dectin-1] that sense pathogens or damaged tissues to trigger innate immune responses.”

Immune Cell Receptor – Micronization / Particle Size / Endocytosis: Keiji H, Hiroshi T, “Endocytosis of Particle Formulations by Macrophages and Its Application to Clinical Treatment,” Chapter 16; 0706 2012. Quote: “Particle size is likely the primary factor that governs endocytic uptake of particles. The optimum size of particles for efficient endocytic uptake varies according to the cell type. Macrophage cells are able to ingest large particles having a diameter between 1 micron and 10 microns to eliminate invaders from outside the body. The optimal sizes of the particles for the uptake by alveolar macrophages [primarily in the lungs] range between 3 microns and 6 microns, but those by peritoneal macrophages and peripheral blood mononuclear cells are reportedly from 0.3 microns to 1.1 microns.” The term micronized in reference to beta 1,3/1,6 glucan particles refers to insoluble particles 5 microns or less in size, with uniformity in micronized particles in size in a dose an important variable. One micron equals 1/25,400th of an inch or 3.93701e-5 of an inch.

Immune Cell Receptor – Dectin-1: Goodridge H, Reyes C, Becker C, et al, “Activation of the innate immune receptor Dectin-1 upon formation of a phagocytic synapse.” Nature, 472(73(7344): 471-478: PMID 21525931, Apr 28, 2011. Quote: “…In this study we show that despite its ability to bind both soluble and particulate B-glucan polymers, Dectin-1 signaling is only activated by particulate B-glucans. …The “phagocytic synapse” now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular anti-microbial responses only when they are required.”

Immune Cell Receptor – Dectin-1 Brown GD, Gordon S, Herre J, Willment JA, “The role of Dectin-1 in antifungal immunity,” Crit Rev Immunol, 24(3):193-203, PMID 15482254, 2004. Quote: “Dectin-1 [C-type lectin-like receptor] is expressed on phagocytic cells, including macrophages and neutrophils, and mediates both the internalization and cellular responses to beta-glucan… . Dectin-1 can recognize and respond to live fungal pathogens…having a key role in the innate responses to these pathogens.”

Immune Cell Receptor – Dectin-1: Williment JA, Brown G, Gordon S, “Characterization of the human beta-glucan receptor and its alternatively spliced isoforms.” J Biool Chem, 43818-23, PMID 11567029, Novem 2001. Quote: “Beta-1,3-d Glucans are biological response modifiers with potent effects on the immune system. The [Dectin-1] human beta-glucan receptor is a type II transmembrane receptor…widely expressed and functions as a pattern recognition receptor [PRR], recognizing a variety of beta-1,3- and/or beta-1-6 linked glucans as well as intact yeast.”

Immune Cell Receptor – Dectin-1: Brown GD, Gordon S, “Immune Recognition. A new receptor for beta-glucans.” Nature, 413(6851):36-37, PMID 11544516, Sep 2001. Quote: “…beta-1,3-d-glucans exert potent effects on the immune system – stimulating antitumour and antimicrobial activity – by binding to receptors on macrophages and other white blood cells and activating them. …Hear we identify this unknown receptor as dectin-1….”

Immune Defense System and Immune Response – See also “Innate Immune Response” Category

Immune Response: Koch JF, Oliveira CA, Zanuzzo FS, “Dietary B-glucan Improves Innate Immune Responses and Disease Resistance in Nile tilapia Regardless of the Administration Period,” S1050-4648(21)00045-0, PMID: 33640538, https://doi.org/10.1016/j.fsi.2021.02.014 , Feb 25 2021. Quote: “This study shows regardless of the administration period (i.e., 15 up to 45 days), the B-glucan improved innate immune responses and the tilapia’s resistance to disease, and this protection could be observed up to 10 days post-feeding trial…These findings…demonstrate that a longer B-glucan feeding protocol may be considered to achieve better results.”

Immune Response: Zou S, Duan BA, Xu X, “Inhibition of tumor growth by B-glucans through promoting CD4 T cell immunomodulation and neutrophil-killing in mice.” Carbohydr Polym, 1:213:370-381. PMID 30879681, June 2019. Quote: “B-glucans…exhibited S-180 tumor-suppressing ability with good safety. B-glucans not only targeted to lymphoid organs and increased CD4 T cells number but also enhanced CD4 T cells and neutrophils populations in tumors. It was proposed that B-glucans promoted CD4 T cell immunomodulation and neutrophils infiltration into tumors, leading to tumor growth inhibition. These findings reveal that B-glucans can be used as an effective agent for cancer immunotherapy.” Notes: CD4 are white immune helper T cells. An S-180 tumor is a sarcoma cancer tumor cell.

Immune Response: Camilli G, Tabouret G, Quintin J, “The Complexity of Fungal B-Glucan in Health and Disease: Effects of Mononuclear Phagocyte System,” Front Immunol, 9:673. PMID 29755450, Apr 2018. Quote: “Study of this molecule [B-glucan] has been motivated by its importance as a pathogen-associated molecular pattern [PAMP] upon fungal infection as well as by its promising clinical utility as a biological response modifier for the treatment of cancer and infectious diseases. Its [B-glucan’s] immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils and natural killer cells.” Note: A Pathogen-associated molecular pattern (PAMP) is a distinct evolutionarily conserved structure on pathogens detected by pattern recognition receptors (PRRs), with PRRS relied upon by the innate immune system in the defense against invading microbial pathogens.

Immune Response: Vetvicka V, Vetvickova I, “Glucans and Cancer: Comparison of Commercially Available B-glucans – Part IV,” Anticancer Res, 38(3):1327-1333, PMID 29491056, Mar 2018. Quote: “Among the well-studied effects of B-glucans, we can mention stimulation of both humoral and cellular immunity, metabolic control of diabetes, stimulation of wound healing, stress reduction, attenuation of chronic fatigue syndrome, lowering cholesterol levels, and inhibition of cancer. …Chronic respiratory problems. In Japan, glucan has been widely used, for over 30 years, in the treatment of gastrointestinal cancer.”

Immune Response Sequence: Rusek P, Wala M, et al, “Infectious Agents as Stimuli of Trained Innate Immunity,” Int J Mol Sci, 19(2):456, https://doi.org/10.3390/ijms19020456, PMID 29401667, Feb 3 2018. Quote: “When the host organism encounters an infectious agent, its immune response is triggered. This mechanism consists of three steps: recognition of a pathogen, response to its activity (immune reaction), and eradication of pathogen from the host organism. Immunity can be divided into innate (non-specific) and acquired/adaptive ([humoral-] specific) responses-both of them are manifested by cellular and humoral mechanisms.

The cellular mechanisms of the innate immunity are characterized by phagocytic [engulfing] and cytotoxic [chemical issuing] activity of cells, while the humoral response is based on the complement system, lysozyme, and acute phase proteins. During humoral response, cells accumulate at the site of pathogen penetration and secrete molecules ( e.g., cytokines), which mediate inflammatory reaction. The complement system supports phagocytosis, rapidly destroys microbial cells, and controls the inflammatory process. …

For example, during training of human monocytes with B-glucan (a component of fungal cell wall) from Candida albicans (a human opportunistic pathogen), the immunity is induced not only against fungi, but also against bacteria, viruses and even parasites. Furthermore, it was observed that training of human monocytes induced by chitin from Saccharomyces cerevisiae …leads to enhanced capacity to eliminate microbes like Candida albicans, Staphylococcus aureus (Gram-positive bacteria), or Escherichia coli (Gram-negative bacteria) compared to non-trained human monocytes.”

Immune Response: Borchani C, Fonteyn F, etc, “Structural Characterization, Technological Functionality, and Physiological Aspects of Fungal B-D-glucans: A Review,” Crit Rev Food Sci Nutr, 56(10:1746-52, PMIC 25830657, Jul 2016: Quote: “Thus, they [(1-3)(1-6)-B-glucans] are effective in inhibiting growth of cancer cells and metastasis and preventing bacterial infection. In humans, B-glucans reduce blood cholesterol, improve glucose absorption by body cells, and so help wound healing.”

Immune Response: Raa J, “Immune modulation by non-digestible and non-absorbable beta-1,3/1,6-glucan,” Microbial Ecology in Health & Disease, Vol 26:1, Issue s3, https://doi.org/10.3402/mehd.v26.27824, May 29 2015. Quote: “Beta-1,3/1,6-glucans are naturally occurring polysaccharides found in the cell walls. ..In purified form, beta-1,3/1,6-glucan functions as a signal that alerts the immune system and prepares it to respond quickly and adequately to infections. [Beta-1,3/1,6-glucan as a] nontoxic, non-allergenic and non-immunogenic molecule enhances wound healing and repairs damage caused by strong light or irradiation. It also supports anti-cancer mechanisms in the body and has beneficial effect on the overall health condition. White blood cells with beta-1,3/1,6 glucan and its specific receptors constitute the backbone of the body’s innate immune system, which is the first line of defense against most infections. …Beta-1,3/1,6 glucans are immune modulating natural products that show the greatest promise as supplements that, by acting on basic mechanisms of immunity, will help to counteract the effects of weakened immunity.

Immune Response: Lee DH, Kim HW, “Innate immunity induced by fungal B-glucans via dectin-1 signaling pathway,” Int J Med Mushrooms, 16(1):1-16,PMID: 24940900, 2014. Quote: “The immunomodulating activities of innate immune cells are augmented by the binding of B-glucans to dectin-1 that is expressed by macrophages or dendritic cells. Upon binding B-glucan, innate immune cells activate adaptive immune cells such as B and T lymphocytes or natural killer cells by secreting various cytokines such as interleukins (IL-4, IL-6) and tumor necrosis factor-α. Water-insoluble B–glucans have stronger immunostimulating activities than their water-soluble counterparts. B-glucans have antifungal activity that is similar to their anticancer activities…”

Immune Response Strengthening-Human Studies Review: Steir H, Ebbeskotte V, Gruenwald J, “Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan,” Nutr J; 13;38, PMID 24774968, https://doi.org/10.1186/1475-2891-13-38 , Apr 28, 2014. Quote: “…several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect. …B-glucans from yeast are recognized by immune cells within the mcosal mucosa, …abay the dectin-1 receptor. Furthermore, followig uptake of B-glucans via dectin-1-stimulated phagocytosis, degradation processes within macrophages may make B-glucans systemically available. It seems that insouble , particulate (1,3)–B-glucans with 1,6 branches are able to activate this cascade, while soluable ones activate the antibody-mediated complement sysem via the CR3 receptor. …Further, numerous studies reported other health benefits of B-glucans, including hepatoprotective, wound healing, weight loss, antidiabetic and cholesterol lowering functions. …Clinical trials performed with dietary insoluble particulate B-glucans have demonstrated positive effects on the immune system.”

Immune Response-Human Studies Review : Samuelson AB, Schrezenmeir j, Knutsen SH, “Effects of orally administered yeast-derived beta-glucans,” Mol Nutr Food Res, 58(1):183-93, PMID 24019098, Jan 2014. Quote: “Yeast-derived beta-glucans are considered immunomodulatory compounds suggested to enhance the defense against infections and exert anticarcinogenic effects. …In human trials, orally administered yeast derived beta-glucans (Y-BG) significantly reduced he incidence of upper respiratory tract infections … . In animal models, oral Y-BG have reduced the incidence of bacterial infections and …enhanced antineoplastic [chemotherapy] agents. …Protective effects toward drug intoxication and ischemia/reperfusion injury [tissue damage when blood supply returns to tissue after period of a lack of oxygen] have also been reported.”

Immune Response – Human Trial-Pathogen Defense: Auinger A, Riede L, Bothe G, Busch R, Gruenwald J, “Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defense against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects.” Eur J Nutr, 52(8):1913-8, PMID: 23340963; PMCID: PMC3832763; Dec 2013. Quote: “in the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)beta-glucan reduced the number of symptomatic common cold infections by 25% compared to placebo. Beta-glucan significantly reduced sleep difficulties caused by cold episode. .. . The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.”

Immune Response: Albeituni SH, Yan J, “The effects of B-glucans on dendritic cells and implications for cancer therapy,” Anticancer Agents Med Chem, 13(5):689-98, PMID 23092290, Jun 2013. Quote: “B-Glucan binding to specific receptors in DCs [dendritic cells] and macrophages triggers their activation and maturation, increases their antigen-presentation ability and enhances the production of proinflammatory cytokines that stimulate the polarization of TH1 or TH17 responses and induces the activation of antigen-specific CD8+ cytotoxic T lymphocytes. …Elucidating the molecular mechanisms of B-glucan-induced signaling in immune cells is essential for the design of new therapeutic strategies against cancer.”

Immune Defense System / Colds Human Clinical Trial: Graugaum H-J, Busch R, Stier H, et al, “A double-blind, randomized, placebo-controlled nutritional study using an insoluble yeast beta-glucan to improve the immune defense system.” Dood Nutr Sci, 3(6):738-746, https://doi.org/10.4236/fns.2012.36100 , June 2012. Quote: “In a placebo-controlled, double-blind, randomized clinical trial, the effect of an insoluble yeast beta-glucan preparation on the incidences of common colds and its effect on common cold symptoms were compared to placebo. …the beta-glucan group had significantly less infections compared to placebo. Beta-glucan significantly reduced the typical cold symptoms (‘sore throat and/or difficulty swallowing’, ‘hoarseness and/or cough’ and ‘runny nose’) as opposed to placebo. The present study demonstrates a prophylactic [preventative] effect of yeast beta-glucan on the occurrence of common colds as opposed to placebo. In addition, when these episodes occurred, they were from the beginning less pronounced and subsided faster.”

Immune Response Potentiation: Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, Bose N, Chan AS, Magee AS, Danielson ME, Weiss A, Vasilakos JP, Underhill DM; “Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’,” IBD and Immunobiolgy Research Institute, Available Oct 28, 2011. Quote: “The ‘phagocytic synapse [of particulate B-glucan]…provides a…mechanism…thereby initiating direct cellular antimicrobial responses only when they are required.” Note: Particulate beta 1,3/1,6 glucan potentiates an immune response when a microbe is directly contacted, but does not stimulate an immune response indiscriminately.

Immune Response: Hyung K, Hong J, Youngsoo K, etc. “Stimulatory Effect of B-glucans on Immune Cells,” Immune Netw, 11(4): 191-195 PMC 3202617, Aug 31, 2011. Quote: “B-Glucans, generally called biological response modifiers, are now recognized as anti-tumor and anti-infective drugs. …B-Glucan has been shown to protect against infection by bacteria, viruses and pathogenic microorganisms. B-Glucan also prevents cancer promotion and progression and has anti-tumor effects with monoclonal antibodies and cancer chemotherapeutics.”

Immune Response: Barsanti L, Passarelli, etc, “Chemistry, physico-chemistry and applications linked to biological activities of B-glucans,” Nat Prod Rep 28(3):457-66, PMID: 2120441, Mar 2011. Quote: “B-Glucans have been shown to provide a remarkable range of health benefits, and are especially important against the two most common conventional causes of death in industrialized countries, i.e. cardiovascular diseases (where they promote healthy cholesterol and blood glucose levels) and cancer (where they enhance immune system functions).”

Immune Response: Bobovcak M, Kuniakova R, “Effect of Pleuran (beta-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes.” Appl Physiol Nutr Metab; 35(6):755-762, WMD, PMID: 21164546, DOI: 10.1139/H10-070; Dec 2010.

Immune Response: Murphy EA, Davis JM, Carmichael MD, “Immune modulating effects of B-glucan,” Curr Opin clin Nutr Meetab Care, 13(6):656-61, PMID 20842027, Nov 2010. Quote: “B-Glucans appear to be effective at enhancing immune function and reducing susceptibility to infection and cancer.”

Immune Response activator-Dectin 1: Kankkunen P, Teirila L, et, “(1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages,” J Immunol, 1;184:(11) 6335-42 PMID: 20421639, Jun 1, 2010

Immune Response: Volman JJ, Ramakers JD, “Dietary modulation of immune function by beta-glucans,” Physiol Behav. 94(2:276-84, WMD, PMID: 18222501, https://doi.org/10.1016/j.phsbeh.2007.11.045; May 2008. Quote: “…dietary beta-glucans may be a useful tool prime the host immune system and increase resistance against invading pathogens.”

Immune Response activators: Chen J, Seviour R, “Medicinal importance of fungal beta-(1->3),(1>6)-glucans”; Mycol Res, Jun:111(Pt 6):635-652; PMID 175903232; Jun 2007: Quote: “Non-cellulosic beta-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. … The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes.”

Immune Response – Activation of White Blood Cells: Czop, Joyce K., “The Role of .beta.-Glucan Receptors on Blood and tissue Leukocytes in Phagocytosis and metabolic Activation”. Pathology and Immunopathology Research; 5:286-296. Harvard Medical School. 1986.

Immune Response – Activation: Czop J.K., Austen K.F., “A B-glucan Inhibitable Receptor on Human Monocytes: Its Identity with the Phagocytic Receptor for Particular Activators of the Alternative Complement Pathway”. Journal of Immunology 134: 1985; 2588-2593. 1985.*

Immune Response potentiation: Thompson IJ, Oyston PC, Williamson DE, “Potential of the beta-glucans to enhance innate resistance to biological agents,” Expert Rev Anti Infect Ther, 8(3):339-52, PMID: 20192687, Mar 2010. Quote: “The beta-glucans…have a long track record of safe use. Due to their immunomodulatory properties, purified beta-glucans have been used clinically as part of a combination therapy for a variety of cancers and their potential anti-infective properties have received attention.”

Immune Response potentiation: Brown G D, Gordon Siamon; “Fungal B-Glucans and Mammalian Immunity.” Sir William Dunn Sch of Pathology, U of Oxford, UK, Immunity, Vol19, 311-316, 2003. Quote: “B-Glucans are structural cell wall polymers of many fungi which possesses immunomodulatory activities. …The innate immune response is essential for the control of fungal infections, and there is increasing evidence that B-glucans are involved in initiating many aspects of this response. The recognition of fungal pathogens occurs through both opsonic (mainly complement) and nonopsonic mechanisms, and as conserved structural components, B-glucans…play an important role in the non-opsonic recognition of these [fungal] pathogens.

Indeed, many of the B-glucan receptors…have been shown to contribute to the recognition and phagocytosis of these organisms [fungal pathogens]. … B-glucans, especially in particulate form, can produce proinflammatory and antimicrobial responses through the TLRs and Dectin-1 [cell receptors for B-glucan]. Many of these responses are required for the control of fungal infections, such as the production of TNF-Alpha, and is an essential early cytokine required for the control of infections with C. albicans, A. fumigatus, C. neoformans, and H capsulatum. This is also true for IL-12, another important anti-fungal cytokine… . Thus B-glucans appear to have an important role in the innate immune response to fungal pathogens and in initiating a protective adaptive response.

…particulate B-glucans can directly activate leukocytes, stimulating their phagocytic, cytotoxic, and antimicrobial activities, including the production of reactive oxygen and nitrogen intermediates. In addition, these carbohydrates [B-glucans] stimulate the production of proinflammatory mediators, cytokines and chemokines such as IL-8, IL1, IL-6 and TNF Alpha. Stimulation by particulate B-glucans also enhances the ability of macrophages to recognize and clear apoptotic [dying or dead] cells….“

Immune Response potentiation: Jordan F, Hunter Jr. KW, Gault R, “Method for preparing small particle size glucan in a dry material,” U.S. Patent 6,476,003. November 2002. Quote: “The greater generation and/or production of NO (Nitric Oxide) demonstrates the enhanced activity of the macrophage with a small particle size glucan which is indicative of an activity level of an immune system. … The measurement of NO production is indicative of an oxidative burst that kills and/or destroys the ingested microbes and/or particles by the macrophage. …As a glucan re-aggregates into particles of greater than one micron in diameter, it appears to pass through an animal or human digestive system without substantially complete absorption.

… As the glucan re-aggregates to a size of greater than one micron in diameter, some of the beneficial effect of the glucan is not achieved because the macrophage receptors are not activated as readily by glucan greater than one micron in diameter because the receptor size on corresponding cells and molecules that accept the glucan is generally about one micron in size. ……The greater percentage phagocytosis demonstrates the enhanced activity of the macrophage and the small particle size glucan’s ability to activate the immune system.”

Immune Response potentiation – Microparticulate Beta Glucan: Hunter KW, Gault RA, Berner MD, “Preparation of microparticulate B-glucan from Saccharomyces cerevisiae for use in immune potentiation.” Letters in Applied Microbiology,” Vol 35 Issue 4, 267-271, PubMed 12358685, October 2002 (commercially MG Beta Glucan). Quote: “…there was evidence that macrophages, key target cells for the immunopharmacological activity of B-glucans, preferentially ingest particles in the 1-2-µ (micron) diameter size range. …Compared with the aggregated [5-100-µ micron diameter] form of B-glucan, the B-glucan microparticles remain in suspension longer for pharmaceutical applications… . Although both aggregated and microparticulate glucans enhanced peritoneal macrophage activation when administered orally in mice, the microparticulate glucan was significantly better than the aggregated form. …This microparticulate beta-glucan …following oral administration at 0.1 mg kg(-1) for 14 d, enhanced phagocytosis of mouse peritoneal macrophages significantly better than did aggregated beta-glucan particles....A microparticulate form of beta-glucan that remains in suspension longer for pharmaceutical applications and has superior immune potentiation characteristics has been developed. [0.1 mg kg(-1)=7.5 mg per day for a 165 lb person]”

Immune Response – Particulate vs Soluble: Ishibashi K, Miura NN, et al, “Relationship between the physical properties of Candida albicans cell well beta-glucan and activation of leukocytes in vitro,” Int Immunopharmacol 2(8):1109-22. Jul 2002. Quote: “Beta-glucan activated leukocytes significantly more effectively in a particulate than solubilized form in terms of TNF-alpha production by RAW 264.7 cells, hydrogen peroxide production by murine PEC and IL-8 production by human PBMC….These facts strongly suggested that the solubility and assembly of the components influence the immunopharmacological activities of 1,3-beta-D-glucans.”

Immune Response potentiation: Hunter K, Gault R, Jordan F, “Mode of Action of B-Glucan Immunopotentiators,” Department of Microbiology, University of Nevada School of Medicine, Oct 1998. Quote: “… the size of a particle is one factor influencing phagocytic [microbe ingestion] efficiency by macrophages. …the number of macrophages actively phagocytosing [ingesting microbes] is affected by the particle size of the glucan. This would suggest that, in vivo, a greater number of macrophages may be activated and thus would provide an enhanced immune response. …these data do indicate that glucan particle size is an important factor in the production of nitric oxide. Nitric oxide is generated during the “oxidative burst” that kills ingested microbes. This would suggest that the small particle glucan [MG Glucan] has greater ability to enhance the immune system than the globular form of glucan.”

Immune System: Ber L., Gazella K., “Activate Your Immune System;” Impakt Communications, 1998.

Immune Response – Small Particle Effectiveness: Hunter K, Gault R, Jordan F, “Mode of Action of B-Glucan Immunopotentiators,” Department of Microbiology, University of Nevada School of Medicine, Oct 1998.

Globular Glucan (μg/ml)

Sonicated Microparticulate Glucan (μg/ml)

Media

Nitric Oxide (μM)

275

600

Quote: “…these data do indicate Glucan particle size is an important factor in the production of nitric oxide. Nitric oxide is generated during the “oxidative burst” that kills ingested microbes [bacteria, viruses, fungi, parasites, etc]. This would suggest that the small particle glucan has greater ability to enhance the immune system than the globular form of glucan.”

Immune Response Potentiator: Jordan, F.; “An Effective Immune Response Potentiator– Beta-1,3/1,6-glucan Derived from Yeast Cell Wall,” Macrophage Technologies Publication, pp 1-7; 1998.

Immune Response – Small Particle Effectiveness: Donzis B. A.; “Substantially purified beta (1,3) finely ground yeast cell wall glucan composition with dermatological and nutritional uses;” U.S. Patent 5702719; 1997. Quote: “The preferred particle size of the find grind glucan product is about 1.0 micron or less and more preferably, .20 microns or less.”

Matsoka, H, Seo Y, et al, “Lentinan potentiates immunity and prolongs the survival time of some patients.” Anticancer Res, 17(4A:2751-5, PMID: 9252710, WMD, Jul-Aug 1997.

Immune Response Enhancement – Oral Dietary Supplement: Matthews, M.; “…Exceptional Immune Enhancing Supplements,” Nutritional Supplement Immuno-Stimulant Bulletin, Vol I, No. 3. 1997.

Immune Response – Increased Survival: Todd, R.F.; “The Continuing Saga of Complement Receptor Type 3 (CR3),” J. Clin Invest.: Vol 98, 1-2. Div of Hematology/Oncology Dept of Int. Med, U of Michigan Med Ctr 1996.* Quote:(p2) “In certain controlled clinical trials, the increased survival of patients receiving these immunostimulatory Beta-glucans has been reported.”

Immune Response: Bodenbach B.; NSC-24™: An Extraordinary New Immune Enhancing Supplement; Health Perspectives, vol 2, no 2; 1996.

Immune Response Enhancement: Meira, D.A., et al; The Use of Glucan as Immunostimulant in the Treatment of Paracoccidioidomycosis; Am J. Trop Med Hyg 55(5), 496-503; Dept of Trop Dis, Dept of Microbio, State U of Sao Paulo, Brazil. 1996. Quote: “…glucan enhances the immune response through stimulation of macrophages by increasing their number, size, and function, stimulates secretion of lysozyme and TNF by activated macrophages, increases the phagocytosis of antigens, activates the formation of granulocyte and monocyte colonies, and factors increased activity of T and B lymphocytes, as well as complement activation.”

Immune Response Enhancement : Spiros J.; Method for immune system activation by administration of a .beta.(1-3) glucan which is produced by Saccharomyces cerevisiae strain R4; U.S. Patent 5504079; 1996.

Immune Response Enhancement Vetvicka V., Thornton B.P., Ross G.D.; “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 Clin Invest 98: 50-61. Div of Experimental Immuno and Immunopath, Dept Path, U of Louisville, KY.* 1996. Quote: “This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity.”

Immune Response – Small Particle Effectiveness: Donzis B. A.; “Substantially purified beta (1,3) finely ground yeast cell wall glucan composition with dermatological and nutritional uses;” U.S. Patent 5576015; 1996. Quote: “Upon oral administration, the smaller or finer particle sized glucan is more quickly dissolved in the gastrointestinal tract and consequently, more readily absorbed.”

Immune Response Enhancement: Rios-Hernandez M., Dos-Santos N.J., Silvia-Cardosa, Belle-Garciga J.L., Peddrosa M., “Immunopharamacological studies of beta(1-3)glucan-1, 3-glucan”, Arch. Med. Res. 25 (2): 179-180. 1994.*

Immune Response Enhancement: Poutsiaka D.D., et al, “Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production,” Blood 82: 3695-3700 ; Dept of Med, New England Med Ctr, Boston, MA. 1993. Quote: “Because of their differential effects on cytokine production, beta-glucans may be used to therapeutic advantage in the diseases in which IL-1 is implicated.”*

Immune Response – Normalization: Chorvatovicova D., Navarova J., “Suppressing effects of glucan on micronuclei induced by cyclophosphamide in mice.” Mutat. Res., 282:147-150, 1992.

Immune Response Enhancement: Sakurai T, Hashimoto K, et al; “Enhancement of murine alveolar macrophage functions by orally administered beta-glucan.” Int. J. Immunopharmacol. 14:821-830. 1992.

Immune Response – T Cell Enhancement: Di Renzo, L., Yefenof, E., Klein E., “The Function of human NK [Killer T] cells is enhanced by B-Glucan, a ligand of CR3 (CD11b/CD18)”. Eur. J. Immunol., 21:1755-1758. 1991.

Immune Response Enhancement: Suzuki, Iwao, Tanaka, Hideki, Konoshita, Akira, Oikawa, Shozo, Osawa, Masumi and Yadomae. “Effects of Orally Administered.beta.-Glucan on Macrophage Function in Mice”. Toshiro, Journal of Immunopharmac; vol. 12, No. 6, pp. 675-684. 1990.

Immune Response – Potentiation: Czop, J.K., Valiante N.M., Janusz M.J.; “Phagocytosis of particulate activators of the human alternative complement pathway through monocyte beta-glucan receptors,” Prog Clin Biol Res 297: 287-296; Dept of Med, Harvard Med S, Boston, MA. 1989. Quote (p1): “Animal studies indicate that beta-glucans with 1,3-and/or 1,6-linkages are active pharmacologic agents that rapidly confer protection to a normal host against a variety of biological insults. The beta-glucan receptors provide a mechanism by which a heightened state of host responsiveness is initiated.”

Immune Response potentiation: Janusz M.J., Austen K.F., Czop J.K.; “Isolation of a Yeast Heptaglucoside that Inhibits Monocyte Phagocytosis of Zymosan Particles”. The Journal of Immunology; 142:959-965. Dept of Med, Harvard Med Sch, Boston, MA.* 1989. Quote: “Beta-Glucans with 1,3-and 1,6 glycosidic linkages are the major structural components of yeast and fungal cell walls and are active pharmacologic agents in host defense systems of plants and animals….The administration of particulate glucans from S. cerevisiae to laboratory animals induces host resistance to a variety of lethal pathogens by mechanisms involving macrophage stimulation.”

Immune Response Enhancement: – Oral Applications: Wyde, P., “Beta-1,3-glucan activity in mice: intraperitoneal and oral applications.” Baylor College of Medicine Research Report. 1989.

Immune Response: Bousquet M., Escoula L. et al; “Immunopharmacologic study in mice of 2 beta-1,3, beta-1,6 polysaccharides (scleroglucan and PSAT) on the activation of macrophages and T lymphocytes,” Ann Rech Vet 20: 165-173. 1Station of Pharmacologie-Toxicologie, INRA, Toulouse, France. 1989.* Quote: “…PSAT and scleroglucan favorably affect the non-specific host defense and cellular immune response in mice.”

Immune Response Potentiation – B Cells: Czop J.K., Puglisi A.V., Miorandi D.Z., Austen K.F.; “Pertubation of beta-glucan receptors on human neutrophils initiates phagocytosis and leukotriene B4 production,” J. Immunol 141: 3170-3176. 1988.*

Immune Response Enhancement – IL 1 & IL 2: 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.

Immune Response Enhancement – IL 1: Rasmussen LT, Seljelid R, “Production of prostaglandin E2 and interleukin 1 by mouse peritoneal macrophages stimulated with beta-1,3-D-glucan derivatized plastic beads,” Scand J Immunol 26(6): 731-736. Dec 1987.*

Immune Response Enhancement: Janusz M.J., Austen K.F., Czop J.K.; “Lysosomal enzyme release from human monocytes by particulate activators is mediated by beta-glucan inhibitable receptors,” J. Immunol 138: 3897-3901. 1987.*

Immune Response – Normalization: Ferencik M, Kotulova D, Masler L, Bergendi, L, Sandula J, Stefanovic J; “Modulatory effect of glucans on the functional and biochemical activities of guinea-pig macrophages.” Methods Find. Exp., Clin. Pharmacol. 8:163-166. 1986.

Immune response Enhancemenet & Macrophage stimulation: Czop J.K., Austen K.F.; “Generation of leukotrienes by human monocytes upon stimulation of their beta-glucan receptor during phagocytosis,” Proc Natl Acad Sci USA; 82: 2751-2755 1985.*

Immune Response Enhancement: Seljelid R., et al.,”In vivo activation of mouse macrophages with beta-1,3-D-glucan-derivatized plastic beads,” Scand J Immunol 21(6):601-605. Jun 1985.*

Immune Response Enhancement Seljelid R., et al., “A Soluble .beta.-1,3-Glucan Derivative Potentiates the Cytostatic and Cytolytic Capacity of Mouse Peritoneal Macrophages In Vitro”. Immunopharmacol; 7: 69-73. 1984.*

Immune Response Enhancement: Kimura A., et al., “In Vitro Activation of Human Adherent Cells by a Glucan, Schizophyllan”. J. Reticuloendothel.; Soc. 34: 1-11. 1983. Quote: “…Glucan-treated rats had significantly increased rates of phagocytosis and killing of Staphylococcus aureus immediately after infection…”

Immune Response – Potentiation: Hunter KW [U Nevada Reno], Fishcer GW, Sayles PC, Strictkland GT; “Levamisole: Potentiation of the primary immunoglobulin M antibody response in suckling rats.;” Immunopharmacology 3:117-127; 1981.

Immune Response – Enhancement: Lotzova and Gutterman, “Effect of Glucan on Natural Killer (NK) Cells: Further Comparison Between NK Cell and Bone Marrow Effector Cell Activities”. J. Immunol., 123: 607-611. 1979

Immune Response – Macrophage Cell Production Increase: Burgaleta C., Territo M.C., Quan C.G., Goide D.W.; Glucan activated macrophages: functional characteristics and surface morphology; J Reticuloendothel Soc 23: 195-204. 1978. Quote: “These studies indicate that glucan administration results in increased granulocyte and macrophage production….glucan as an immunotherapeutic agent can result in an increased number of available effector cells.“

Immune Response – Macrophage Cell Production Increase : Burgaleta, C. and Golde, D.W.; “Effect of Glucan on Granulopoiesis and Macrophage Genesis in Mice”. Cancer Research; 37:1739-1742; Jun 1977.*

Immune Response – Enhancement & Stimulation: DiLuzio N.R., et al., “Evaluation of the Mechanism of Glucan-Induced Stimulation of the Reticuloendothelial System”. J. Reticuloendothelial Soc.; Soc.7: 731-742. 1970..

Immune Response Enhancement: Wooles and DiLuzio N.R.; “The Phagocytic and Preoperative Responses of the Reticuloendothelial System Following Glucan Administration”. J. Reticuloendothelial..; Soc. 1: 169-169. 1964.

Immune Training

Immune Training: Heng Y, Zhang X, et al, “Systemic administration of B-glucan induces immune training in microglia,” J Neuroinflammation,18(1):57, PMID: 33618716, https://doi.org/10.1186/12974-021-02103-4, Feb 22 2021. Quote: “Our results demonstrate that preconditioning with BG [Beta glucan] …induced immune training of microglia at two days after the first challenge.”

Immunizations – Adjuvant: See also “Adjuvant”

Immunizations – Adjuvant: Hunter KW Jr, Berner VK, Sura ME; “Conjugation of protein antigen to microparticulate beta-glucan from Saccharomyces cerevisiae: a new adjuvant for intradermal and oral immunizations,” Dept of Microbiology and Immunology, U of Nev Sch of Medicine, Reno, NV 89557, USA. Appl Microbiol Biotechnol; PuMed 18677470; Epub Aug 2, 2008: Quote: “Our laboratory has prepared and characterized a novel microparticulate beta-glucan (MG)…we hypothesized that MG could serve as a vaccine adjuvant to enhance specific immune responses. …When used to immunize mice by the intradermal route, these conjugates enhanced the primary IgG antibody response to BSA in a manner comparable to the prototypic complete Freund’s adjuvant....These results suggest that protein antigens can be conjugated to MG via a carabondiimide linkage and that these conjugates provide an adjuvant effect for stimulating the antibody response to the protein antigens.”

Immunoadjuvant: see “Adjuvants”

Immunocompromised: Adjuvant: Beta Glucan Ikewaki N, Dedeepiva VD, et al, “B-glucan vaccine adjuvant approach for cancer treatment through immune enhancement in specific immunocompromised populations,” 47(1):14, PMID: 34779494, https://doi.org/10.3892/or.2021.8225 , Nov 15, 2021. Quote: “The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side-effects. Previous studies have reported that chronic microinflammation, with occurs in disease, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread.

The aim of the present review was to provide evidence of a biological response modifier B-glucan [B-glucan vaccine adjuvant approach for treating cancer via immune enhancement and its beneficial effects], including vaccine-adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggest its [B-glucan vaccine adjuvant approach] value as a potential strategy to provide long-term prophylaxis in immunocompromised individuals or genetically prone to cancer.”

Immunoglobulin – IgA-Colds/Flu-Human Study: McFarlin BK, Carpenter KC, Davidson T, “Baker’s yeast beta glucan supplementation increases salivary IgA [immunoglobulin] and decreases cold/flu symptomatic days after intense exercise,” J Diet Suppl 10(3):171-83, PMID: 23927572. Sept 2013. Quote: “BG [beta glucan] was associated with a 37% reduction in the number of cold/flu symptom days postmarathon compared to placebo (p = .026). In E2, BG was associated with a 32% increase in salivary IgA [immunoglobulin A].” Note: Immunoglobulin A is an antibody that plays a critical role in immune function in the mucous membranes.

Immunomodulator – Beta Glucan: Vetvicka V, Vannucci L, Sima P, Richter J, “Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials,” Molecules, 24(7), 1251; doi 10.3390/molecules24071251, PMID: 30935016, Mar 30, 2019. Quote: “Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. …With more than 80 clinical trials evaluating their biological effects..[and] With over 20,000 published studies, glucan has the best position among other immunomodulators. …An immunomodulator is defined as the substance capable of interacting with the immune system resulting in up- or down-regulating specific parts of the immune response.”

Immunomodulator-surgical patients-Clinical Trial: Babineau TJ, Hackford A, et al: “A phase II multicenter, double blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in [67] high risk surgical patients,” Archi Surg, 129(11):1204-10; PMID 7979954, Nov 1994. Quote: “PGG-glucan was generally safe and well tolerated, may decrease postoperative infection rates, and warrants further investigation… .”

Imunonutrition: Nieman DC, “Immunonutrition support for athletes,” Nutr Rev, 66(6):310-320,WMD, 2008.

Imunostimulatory Activity -: Hunter K, Washburn R, “Efficacy of topical antimicrobial acid and immunostimulatory B-Glucan in Animal Models of Cutaneous Infection,” U Nevada Medical School-Applied Res Grant, Aug 1998. Quote: “…the B-glucans have been shown to activate macrophages to enhance their antimicrobial activity. Our laboratory has developed preliminary evidence that B-1,3/1,6 glucans possesses immunostimulatory activity for macrophages in vitro, leading to secretion of the Th-1 cytokines IL-1 B, IL-12, and TNF-µ.”

Immunosuppression – Chemotherapy – Chae JS, Shin H, et al, “Yeast (1-3)-(1-6)-B-d-glucan alleviates immunosuppression in gemcitabine-treated mice”, Intl J Biol Macromoi, SO141-8130(19)32692-3, PMID: 31170489, June 3 1019. Quote: “Gemcitabine is one of he most effective chemotherapy drugs commonly used for treatment of various tumors. …the main toxicity of gemcitabine is myelosuppression [immunosuppression] , which not only reduces patient quality of life, but also hinders further anticancer treatment. …immunotherapy can address these drawbacks because of its ability to enhance the patient’s immune system. …In conclusion, yeast B-glucans have the potential to be used as adjuvants for alleviating chemotherapy-induced immunosuppression in patients.” Note: “myeolosuppression” is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. When severe it is “myeloablation.” Immunosuppression is lessening of the immune response of which myeolosuppression is a form.

Immunosuppression – Tumors: Qi C, Cai Y, Ding, Li B, Kloecker G, Qian K, Vasilakos J, Saijo S, Iwakura Y, Yannelli JR, Yan J; “Differential pathways regulating innate and adaptive antitumor immune responses by particulate.” Div of Hermatology/Oncology, Dept of Medicine, James Graham Brown Ctr, U of Louisville, KY; Blood;117(25):6825-36; Jun 23, 2011. Quote: “B-glucans have been reported to function as a potent adjuvant to stimulate innate and adaptive immune responses. …Here we show that yeast-derived B-glucan activated dendritic cells (DCs and macrophages)....Activated DCs by particulate B-glucan promoted Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. Treatment of orally administered yeast-derived particulate B-glucan elicited potent antitumor immune responses and drastically down-regulated immunosuppressive cells, leading to the delayed tumor progression.” Note: Type 1 T helper (Th1) cells produce interferon-gamma, interleukin (IL)-2, and Lymphotoxin-alpha (formerly known as tumor necrosis factor – beta or TNF-β), which activate macrophages and are responsible for cell-mediated immunity and phagocyte-dependent protective responses.

Immunotherapy:

Immunotherapy – Carrier – Drug Delivery System: Yuting S, Chen L, Yang F, Cheung PCK, “Beta-d-glucan-based drug delivery system and its potential application in targeting tumor associated macrophages [TAMS]”, Carbohydr Polym,253;117258, PMID: 33278940, DOI: 10.1016/1-carbpol.2020.117258, Feb 1 2021. Quote: “B-d-glucans can be developed as promising carriers for targeting delivery with stability, biocompatibility and specificity when applied in immunotherapy. Targeting tumor associated macrophages (TAMs) is an emerging strategy for cancer immunotherapy since it exerts anti-cancer effects based on modulating body immunity in tumor microenvironment (TME). This new strategy does not require high concentration of drugs to kill cancer cells directly and lessen tumor recurrence by creating unique immune memory for malignant cells.”

Immunotherapy – Chemotherapy-colon cancer: Cheng H, Sun L, “Beta-1,6 glucan converts tumor-associated macrophages into an m1-like phenotype.” Carbohydr Polym, 247:116715, PMID: 32829842, DOI: 10.1016/j.carbpol.2020.116715, Nov 1, 2020. Quote: “Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to immunosuppression and resistance to chemotherapies of cancer, thus targeting TAMs has been an attractive therapeutic strategy to cancer immunotherapy. …The present study showed that the B-1,6-glucan could promote the transformation of M2-like macrophages to M1-like phenotype and inhibit the viability of colon cancer cells in vitro and in vivo.”

Immunotherapy: Cancer: Gelter A, Shrestha R, et al, “Yeast-Derived B-Glucan in Cancer: Novel Uses of a Traditional Therapeutic,” Int J Mol Sci, 20(15), PMID: 31344853, Jul 24 2019. Quote: “Therapeutics that render the TME [tumor microenvironment] immune-reactive have a vast potential for establishing effective cancer interventions. One such intervention is B-glucan, a natural compound with immune-stimulatory and immunomodulatory potential that has long been considered an important anti-cancer therapeutic. B-glucan has the ability to modulate the TME both by bridging the innate and adaptive arms of the immune system and by modulating the phenotype of immune-suppressive cells to be immune-stimulatory.

…B-glucan is involved in a concept called trained immunity, where innate cells take on memory phenotypes. Additionally, the hollow structure of particulate B-glucan has recently been harnessed to utilize particulate B-glucan as a delivery vesicle. …B-glucan may play an essential role in futures strategies to prevent and inhibit tumor growth.”

Immunotherapy – Chemotherapy – Chae JS, Shin H, et al, “Yeast (1-3)-(1-6)-B-d-glucan alleviates immunosuppression in gemcitabine-treated mice”, Intl J Biol Macromoi, SO141-8130(19)32692-3, PMID: 31170489, June 3 2019. Quote: “Gemcitabine is one of he most effective chemotherapy drugs commonly used for treatment of various tumors. …the main toxicity of gemcitabine is myelosuppression, which not only reduces patient quality of life, but also hinders further anticancer treatment. …immunotherapy can address these drawbacks because of its ability to enhance the patient’s immune system. …In conclusion, yeast B-glucans have the potential to be used as adjuvants for alleviating chemotherapy-induced immunosuppression in patients.” Note: “myeolosuppression” is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. When severe it is “myeloablation.” Immunosuppression is lessening of the immune response of which myeolosuppression is a form.

Immunotherapy: Zou S, Duan BA, Xu X, “Inhibition of tumor growth by B-glucans through promoting CD4 T cell immunomodulation and neutrophil-killing in mice.” Carbohydr Polym, 1:213:370-381. PMID 30879681, June 1 2019. Quote: “B-glucans…exhibited S-180 tumor-suppressing ability with good safety. B-glucans not only targeted to lymphoid organs and increased CD4 T cells number but also enhanced CD4 T cells and neutrophils populations in tumors. It was proposed that B-glucans promoted CD4 T cell immunomodulation and neutrophils infiltration into tumors, leading to tumor growth inhibition. These findings reveal that B-glucans can be used as an effective agent for cancer immunotherapy.” Notes: CD4 are white immune helper T cells. An S-180 tumor is a sarcoma cancer tumor cell.

Immunotherapy: Cancer – Jin Y, LiP, Wang F, “B-glucans as potential immunoadjuvants: A review on the adjuvanticity, structure-activity relationship and receptor recognition properties,” Vaccine, 36(35: 5235-5244, PMID: 30049632, Aug 23 2018. Quote: “…B-glucans have been studied as adjuvants in anti-infection vaccines as well as immunomodulators in anti-cancer immunotherapy. B-glucans can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines. When B-glucans act as immunostimulants or adjuvants, a set of receptors have been revealed to recognize B-glucans, including dectin-1, complement receptor 3 (CR3), CD5, lactosylceramide, and so on.”

Immunotherapy: Cancer – Zhang M, Kim JA, Huang AY, “Optimizing Tumor Microenvironment [TME] for Cancer Immunotherapy: B-Glucan-Based Nanoparticles,” Front Immunol, 9:341, PMID: 29535722, Feb 26 2018. Quote: “Emerging data suggest that the TME [Tumor Microenvironment for Cancer Immunotherapy] can be actively manipulated by B-glucans and their related nanoparticles.

Immunotherapy: Ning Y, et al, “B-glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses.” Int J Cancer, 1:138(11): 2713-23, PMID:26773960. June 1, 2016. Quote: “Treatment with β-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that β-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for β-glucan in immunotherapy.”

Immunotherapy : Tian J, Ma J, Ma K, etc, “B-Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid-derived suppressor cells.” Eur J Immunonl, 2013 May;43(5):1220-30. Quote: “Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a major role in tumor-induced immunosuppression, which hampers effective immuno-therapeutic approaches. B-Glucans have been reported to function as potent immune-modulators to stimulate innate and adaptive immune responses, which contribute to their antitumor property. …thereby leading to the delayed tumor progression.”

Immunotherapy: LiB, Cai Y, Qi C, etc., “Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer.” Clin Cancer Res, 16(21):5153-64.. Nov 1 2010. Quote: “IFN-y [interferon] production of tumor-infiltrating T cells and CTL responses were significantly enhanced on B-glucan treatment, which ultimately resulted in significantly reduced tumor burden. …These data highlight the ability of yeast-derived B-glucan to bridge innate and adaptive antitumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy.”

Immunotherapy: Cabezas J, Albaina O, et al, “Potential of anti-Candida antibodies in immunoprophylaxis,” Immunotherapy, 2(2):171-183, WMD, 2010.

Immunotherapy: Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E; “Effects of beta-glucans on the immune system.” Medicina (Kaunas). Dept of Physiology, Kaunas U of Medicine, Kaunas, Lithunia. 43(8):597-606; 2007. Quote: “Beta-glucans are naturally occurring polysaccharides….These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. Beta-Glucans also show anti carcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, beta-glucan can inhibit tumor growth…reduce tumor proliferation, prevent tumor metastasis. beta-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis [red blood cells] following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These [monoclonal] antibodies activate complement system and opsonize tumor cells with iC3b fragment. …tumor cells, as well as other host cells, lack beta-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism [tumor-killing activity] could be induced in the presence of beta-glucans.”

Immunotherapy:: Li B, Allendorf D, Hansen R, Marroquin J, Ding C, Cramer DE, Yan J; “Yeast beta-Glucan Amplifies Phagocyte Killing of iC3b-Opsonized Tumor Cells via Complement Receptor 3-Syk-Phosphatidylinositol 3-Kinase Pathway.” J Immunology: 1:177(3):1661-9. Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY. Aug 2006. Quote: “Anti-tumor mAbs [monoclonal antibodies] hold promise for cancer therapy, but are relatively inefficient. …In this study, we report that tumor-bearing mice treated with a combination of beta-glucan and an anti-tumor mAb show almost complete cessation of tumor growth. … beta-glucan, an agent without evident toxicity, may be used to amplify tumor cell killing and may open new opportunities in the immunotherapy of cancer.”

Immunotherapy: Hong F, Yan J, ”Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models.” J Immunol 173(2):797-806, PMID 15240666. Jul 15 2004. Quote: “Orally administered B-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. …Antitumor mAb [monoclonal antibodies] bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast beta-1,3;1,6-glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b complement) receptors (CR3; CD11b/CD18) of circulating granulocytes [primarily neutrophils] , enabling CR3 to trigger cytotoxicity [emitted chemical killing] of iC3b-coated tumors. “

Impaired Immunity: Carrow, D.J. M.D.; “Beta-1,3-glucan as a Primary Immune Activator,” Townsend Letter; June 1996. Quote: “The following list includes benefits from the use of Beta 1,3-glucan supplementation: People who have impaired immunity from any cause including, but not limited to HIV infection; have a high occurrence of infectious diseases; have tumors and/or those undergoing chemotherapy or radiation therapy; are over forty who are concerned about the natural aging process or might have noticed a slowing down of immune reactivity; who are geriatric patients; and other with compromised immune disorders. … In vitro studies reveal that bone marrow-derived mouse macrophages and human peripheral blood monocytes possess Beta-glucan receptors that mediate phagocytosis of glucan particles and induce release of proinflammatory mediators…”

Infections – Beta Glucan

Infections: Vetvicka V, Vetvickova J, “Anti-infectious and Anti-tumor Activities of B-glucans,” Anticancer Research. Vol 40, No. 6 3139-3145, doi:10.21873/anticanres.14295, PMID: 32487608, June 2020. Quote: “From the current and previous studies, we can clearly confirm that glucans have significant immuno-stimulating, anti-infectious, and anti-cancer effects.”

Infection: Sepsis-Trauma: , McBride MA, Owen AM, Stothers CL, et al; “The Metabolic Basis of Immune Dysfunction Following Sepsis and Trauma,” Front Immunol;11:1043. PMID: 3254753, DOI: 10.3389/fimmu.2020.01043, May 29 2020. Quote: “Serious infection …frequently precipitates sepsis, a complex disease spectrum that includes systemic inflammation and organ dysfunction. As such, sepsis is the leading cause of death in non-cardiac intensive care units (ICU). … Stimulation of innate immune cells … such as [macrophages, neutrophils et al] …[by] B-glucan reprograms their metabolism, which supports …antimicrobial capacity to combat invading infections. … Glucans are potent immunomodulators that augment host resistance against gram negative [Escherichia coli], gram positive (Staphylococcus aureus), fungal [Candida albicans] and parasitic infections. Further, glucan has been shown to decrease infectious complications in high risk surgical patients.”

Infection – Mycobacterium Tuberculosis: Moorlag SJCFM, Khan N, Novakovimyelopoic B, “B-Glucan Induces Protective Trained Immunity Against Mycobacterium Tuberculosis Infection: A Key Role for IL-1,” Cell Rep. 19;31(7):107634. doi: 10.1016/j.celrep.2020.107634; PMID: 32433977, May 19 2020. Quote: “B-glucan is a potent inducer of epigenetic and functional reprogramming of innate immune cells, a process called “trained immunity,” resulting in an enhanced host response against secondary infections. …Mice treated with B-glucan are significantly protected against pulmonary Mtab [Mycobacterium tuberculosis] infection, which is associated with the expansion of hematopoietic stem and progenitor cells in the bone marrow and increased myelopoiesis. The administration of B-glucan may be used as a novel strategy in the treatment of mycobacterial infections and possibly as an adjuvant to improve anti-tuberculosis vaccines. Note: “myelopoiesis” refers to production of bo

Infection – Herpes-simplex 1 Virus – Human Trial: Urbancikova I, Hudackova D, et al, “Efficacy of Pleuran ( B-[1,3/1,6] glucan [insoluble] rom PLeurotus ostreatus) in the Management of Herpes Simplex Virus Tpe 1 Infection,” doi: 10.1155/2020/8562309, PMID: 32419831, Apr 13 2020. Quote: “One of the highly prevalent viral pathogens among children and adults causing infection…is herpes simplex virus type 1 (HSV-1). …Therefore the development of natural drugs with low toxicity that are able to enhance host antiviral defense against HSV infection is needed. B-Glucans represent a type of biologically active molecules possessing antiviral properties. …Active treatment with pleuran [Beta 1,3/1,6 glucan] …caused a significantly shorter duration of herpes simplex symptoms compared to the placebo group.”

Infections – Beta Glucan: Dos Santos JC, Barroso de Figueiredo AM, et al, “B-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32″, Cell Rep, 28(10):2659-2672, PMID: 31484076, Sep 3 2019. Quote: “American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection …via a process called trained immunity, conferring non-specific protection from secondary infections. …monocytes trained with the fungal cell wall component B-glucan confer enhanced protection against infections caused by Leishmania brazillensis through the enhanced production of proinflammatory cytokines.”

Infections – Beta Glucan: Vetvicka V, Vannucci L, Sima P, Richter J, “Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials,” Molecules, 24(7), 1251; doi 10.3390/molecules24071251, PMID: 30935016, Mar 30, 2019. Quote: “…glucan has been established in protection against infection. The protective effects of glucan application were shown in experimental models of infection with Leishmania major, L. donovani, Candida albicans, Toxoplasma gondii, Streptococcus suis, Plasmodium berghei, Staphylococcus aureus, Escherichia coli, Mesocestoides corti, Trypanosoma cruzi, Eimeria mermiformis, and Bacillus anthracis.“

Infections: Camilli G, Tabouret G, Quintin J, “The Complexity of Fungal B-Glucan in Health and Disease: Effects on the mononuclear Phagocyte System,” Front Immunol, 16:9:673, PMID 29755450, Apr 16, 2018, Quote: “Study of this molecule [B-glucan] has been motivated by its importance as a pathogen-associated molecular pattern upon fungal infection as well as by its promising clinical utility as biological response modifier for the treatment of cancer and infectious diseases. Its immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils and natural killer cells…B-glucans exhibit antitumor and antimicrobial activities by modulating the biologic responses of mononuclear phagocytes [macrophages et al].” Note: A Pathogen-associated molecular pattern (PAMP) is a distinct evolutionarily conserved structure on pathogens detected by pattern recognition receptors (PRRs), with PRRS relied upon by the innate immune system in the defense against invading microbial pathogens.”

Infection-Reinfection-Trained Immunity: Garcia-Valanen, Guzman-Genuino RM, et al, “Evaluation of Trained Immunity by B-1,3(D)-Glucan on Murine Monocytes in Vitro and Duration of Response in Vivo,” Immunol Cell Biol, 95(7) 601-610, PMID 28228641, Aug 2017. Quote: “The B-1,3(d)-glucan present in the cell wall of Candida albicans induces epigenetic changes in human monocytes resulting in primed macrophages exhibiting increased cytokine responsiveness to reinfection. This phenomenon is referred to as trained immunity or innate immune memory.”

Infection: Raa J, “Immune modulation b non-digestible and non-absorbable beta-1,3/1,6-glucan,” Micro Edo in Heal & Disease, Vol 26:1, Issue s3, DOI: 103402/mehd.v25.27824, May 29 2015. Quote: “Due to their ability to enhance infection defense mechanisms and simultaneously down-regulate inflammations, beta-1,3/1,6-glucan is very promising as an alternative to the mainstream use of immunosuppressive drugs to treat inflammatory diseases, for instance, IBD.

Infection: 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, PMID 21609131. Jun 7 2011. Quote: “The pharmacological capabilities of 1,3-B-glucans include the impartation of tumor inhibition, resistance to infectious disease, and improvements in wound healing.”

Infection: Murphy EA, Davis JM, Carmichael MD, “Immune modulating effects of B-glucan,” Curr Opin clin Nutr Meetab Care, 13(6):656-61, PMID 20842027, Nov 2010. Quote: “B-Glucans appear to be effective at enhancing immune function and reducing susceptibility to infection and cancer.”

Infection: Vetvicka V; “Glucan-immunostimulant, adjuvant, potential drug,” World J Clin Oncol, 2(2):115-119 Feb 10 2010. Quote: “The significant role of glucans in cancer treatment, infection immunity, stress reduction and restoration of damaged bone marrow has already been established.”

Infection: Chen J, Seviour R, “Medicinal importance of fungal beta-(1–3), (1–6)-glucans” Mycol Res 111(Pt6):635-52, PMID 17590323, Jun 2007. Quote: “The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes.”

Infection – intrauterine: Singh U, Nicholson G, et al; “Immunological properties of human decidual macrophages – a possible role in intrauterine immunity,” Reproduction;129(5):631-7, Nuffield Dept. of Obstetrics and Gynaecology, U of Oxford, UK; May 2005. Quote: “These results suggest a role for decidual (uterine mucous wall) macrophages in pathogen recognition and clearance during pregnancy, and, therefore, they are likely to protect the fetus against intrauterine infections which might otherwise lead to preterm labour.” Note: Beta 1,3/1,6-d glucan normalizes and potentiates the macrophage immune cells and is referenced in the complete study.

Infections – secondary: Gu YH, Takagi Y, et al; “Enhancement of radioprotection and anti-tumor immunity by yeast-derived beta-glucan in mice,” J Med Food. 8(2) 154-8; Dept of Radiological Technology, Suzuka U of Med Sc, Suzuka, Japan, Summer 2005. Quote: “Intraperitoneal injection of beta-glucan was shown to greatly delay mortality in mice exposed to whole-body X-ray radiation and tumor growth in tumor-bearing mice. ...Augmented immunological activity as seen in increased NK (natural killer) and LAK (lymphokine-activated killer) activity by beta-glucan seems to play a role in preventing secondary infections associated with irradiation and probably contributes to the attenuated [reduced] tumor growth in tumor-bearing mice through enhanced anti-tumour immunity. These results suggest that beta-glucan may be a promising adjunct treatment for cancer patients receiving radiotherapy.”

Infections – Viral: Jung K, Y Ha, et al, “Antiviral Effect of Saccharomyces Cerevisiae Beta-Glucan to Swine Influenza Virus by Increased Production of Interferon-Gamma and Nitric Oxide,” Clinical Trial, J V”et Med & B Infect Dis Vet Public Health 51(2) 72-6, PMID: 15030604, Mar 2004. Quote: “Saccharomyces cerevisiae beta-glucan reduced the pulmonary lesion score and viral replication rate by SIV [swine influenza virus] -infected pigs. These findings support the potential application of beta-glucan as prophylactic [preventive]/treatment agent in influenza virus infection.”

Infections: 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. Quote: “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.”

Infection: Hunter Jr KW, Gault R, Jordan FM, “Mode of Action of B-Glucan Immunopotentiators-Research Summary Release,” Department of Microbiology, University of Nevada School of Medicine, Jan 2001. Quote: “MG Glucan has been shown to enhance the envelopment and digestion (phagocytosis) of pathogenic microorganisms that cause infectious disease…Laboratory studies have revealed the new MG Glucan is significantly effective at activating Macrophages, and via the Macrophages, the entire immune cascade including T-Cells and B-Cells.”

Infection – Staphyloccus: Dernodle D, Gates H, Kaiser A, “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,”Antimicrob Agents Chemother, 42:3,545-9. Mar 1998. Quote: “…glucan reduces the risk of staphylococcal abscess formation. Neutrophil-activating agents [glucan] are a novel means of prophylaxis against surgical infection and may be less likely than antibiotics to be affected adversely by the increasing antibiotic resistance of nosocomial pathogens.”

Infection-M bovis,BCG: Hetland G, Wiker H, “Protective effect of beta-glucan against mycobacterium bovis, BCG infection in BALB/c mice.” Scand J Immunol, 47:6, 548-53, Jun 1998. Quote: “Beta 1,3-glucan is a potent stimulator of macrophage functions and has a protective effect against a range of infections in rodent models.”

Infection – Viral: Jordan, F.; “An Effective Immune Response Potentiator– Beta-1,3/1,6-glucan Derived from Yeast Cell Wall,” Macrophage Technologies Publication, pp 1-7; 1998.

Infection – Oral Tissue: Ostroff, G.R.; “Inhibition of infection-stimulated oral tissue destruction by .beta(1-3)glucan.(1,3)-glucan,” U.S. Patent 5622940. Issued April 22, 1997.

Infection – Periapical Bone Resorption :Stashenko, et al., “Reduction of Infection-Stimulated Periapical Bone Resorption by the Biological Response Modifier PGG Glucan”, J. Dent. Res.; 74(1):323-330; Dept of Cytokine Biology, Forsyth Dental Ctr, Boston, MA. 1995.* Quote: “PGG glucan-treated animals had significantly less infection-stimulated periapical bone resorption than control animals…”

Infection-Post Surgery: Babineau, et al., “Randomized Phase I/II Trial of a Macrophage-Specific Immunomodulator (PGG-Glucan) in High Risk Surgical Patients”, Annals of Surgery; 220:(5):601-609. Dept of Surgery, Deaconess Hospital, Harvard Medical Sch, Boston MA.* 1994. Quote: “PGG-glucan is safe and appears to be effective in further reduction of the morbidity and cost of major surgery.”*

Infections – Surgical Procedures: Norton MD, JA [Prof of Surg, Chief of Endocrine and Oncologic Surgery]; “Editorial: Annals of Surgery,” Washington University School of Medicine, Nov 1994. Quote: “In a prospective, randomized double-blind study, [Babineau, et.al.] demonstrate that the perioperative administration of PGG-glucan, a substance derived from yeast that increases the microbial killing activity of leukocytes, can decrease infectious complications in patients undergoing major surgical procedures…the preliminary results are positive and should be interpreted as good news.”

Infection – Prevention: 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. Quote: “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 instances 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.”

Infection – Multiple Trauma: De Felippe Junior, et al. ”Infection prevention in patients with severe multiple trauma with the immunomodulator eta 1-3 polyglucose (glucan).” Surgery, Gynecology and Obstetrics; 177(4):383-388. 1993.

Infection – Escherichia coli : 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. Dept of Pathology, Channing Lab, Brigham and Women’s Hospital, Boston, MA. 1992.* Quote: “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.”

Infection: Bacterial: Franek J, Malina J, Kratka H, “Bacterial infection modulated by glucan: a search for the host defense potentiation mechanisms,” Folia Microbiol (Praha) 37(2): 146-152. 1992.*

Infections – Bacterial: 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. Inst of Med Bio, U of Tromso, Norway. 1991.* Quote: “Beta-1,3-D-polyglucose derivatives protect mice against otherwise lethal bacterial infections.”

Infection – Microbial: Raa J., Roerstad G., Engstad R., Robertsen B., “The Use of Immunostimulants to Increase Resistance of Aquatic Organisms to Microbial Infection”. J. Dermatol. Surg. Oncol., (1989) 15:1199-1202. 1989.

Infection – Abdominal: Bowers GJ, Patchen ML, et al, “Glucan enhances survival in an intraabdominal infection model,” J Surg Res 47(2): 183-188; Aug 1989.*

Infection – Postplenectomy : Browder IW.,et al., “Protective Effect of Nonspecific Immunostimulation in Post Splenectomy Sepsis”. J. Surg. Res.; 35: 474-479. Dept of Surg and Physiol, Tulane U Sch of Med, LA. 1983. * Quote: “This study reports the use of glucan, a beta-1,3-polyclucose, as a nonspecific immunostimulant for postsplenectomy pneumococcal sepsis. …Nonspecific immunostimulation appears to have significant potential as a treatment strategy against postsplenectomy infection.”

Infection – Staphylococcus aureus: Kimura A., et al., “In Vitro Activation of Human Adherent Cells by a Glucan, Schizophyllan”. J. Reticuloendothel.; Soc. 34: 1-11. 1983. Quote: “…Glucan-treated rats had significantly increased rates of phagocytosis and killing of Staphylococcus aureus immediately after infection… .”

Infections – Disease: Glovsky MM, et al,; “Effects of particulate beta-1,3 glucan on human, rat, and guinea pig complement activity,” J. Reticuloendothel Soc. 33:401-413. 1983.* Quote: “Glucan administration is associated with the modification of a variety of experimentally induced infectious disease states as well as the inhibition of growth of implantable and spontaneous tumors.”

Infection – Plasmodium Benghei : Holbrook T.W., et al., “Glucan-Enhanced Immunogenicity of Killed Erythrocylic Stages of Plasmodium Benghei”; Infection and Immunity, 32, 542. 1981.

Infection – Diseases: Reynolds J.A., et al., “Glucan-Induced Enhancement of Host Resistance to Selected Infectious Diseases”, Infection and Immunity; 30, 51. 1980.*

Infection – Venezuelan equine encephalomyelitis (VEE): Reynolds JA, Kastello MD, Di Luzio NR, et al, “Glucan-induced enhancement of host resistance to selected infectious diseases,” Infect Immun (1):51-7, PMID 7439978, Oct 30 1980. Quote: “Intravenous pretreatment of mice with glucan significantly enhanced the survival of mice challenged with either Venezuelan equine encephalomyelitis (VEE) virus or Rift Valley fever virus.”

Infection – Staphylococcus Aureus : DiLuzio N.R., Williams DL; “Enhancement of host susceptibility to Staphylococcus aureus infection by chronic ethanol ingestion—modification by glucan immunostimulation,” Alcohol Clin Exp Res 4(3): 254-260. Jul 1980.* Quote: “The administration of glucan significantly prolonged survival of S. Aureus infected control and chronic ethanol mice.”

Infection – Staphylococcus: DiLuzio N.R. and Williams D.L., “Glucan-Induced Modification of the Increases Susceptibility of Cyclophosphamide-Treated Mice to Staphylococcus aureus Infection”. Cancer Immunol. Immunother.; 6: 73-79. 1979.

Infection – Staphylococcus: DiLuzio N.R., Williams D.L., et al, “Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan,” Int J Cancer, 24(6):773-779. Dec 1979.* Quote: “…these studies demonstrate that a soluble glucan preparation exhibits significant anti-tumor and anti-staphylococcal activity.”

Infections – Bacterial: Kokoshis P.L., Williams D.L., Cook J.A., Di Luzio N.R.; Increased resistance to Staphylococcus aureus infection and enhancement in serum lysozyme activity by glucan. Science 199: 1340-1342, 1978.* Quote: “These studies indicate that glucan confers an enhanced state of host defense against bacterial infections.”

Infection – Streptococcus : Mansell P.W.A., Inai, et al., Activation of the Alternative Complement Pathway by Water-Insoluble Glucans of Streptococcus mutans: the Relation Between Their Chemical Structures and Activating Potencies”. Macrophage-Mediated Destruction of Human Malignant Cells In Vitro; Inai et al., J. Immunol (1976); 1256-1260. 1976.

Inflammation

Inflammation -Necrotizing enterocolitis: Zhang X, Zhang Y, He Y, et al, “B-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota, “ J Transl Med, 21(1) PMID: 36627673, https://doi.org/10.1186/s12967-022-03866-x , Jan 10, 2023. Quote: ” Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality … . B-glucan has manifested …anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. “

Inflammation – Colorectal Cancer {CAC]: Yewen X, Shao F, et al, “Whole B-glucan particle attenuates AOM [azoxmehtane]/DSS [dextran sodium sulfate]-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation,” Front Pharmacol, 14:1017475, PMID: 36713833, https://doi.org/10:3389/fphar.2023.1017475 , Jan 12, 2023.

Quote: “Yeast B-glucan is a polysaccharide purified from the Saccharomyces cerevisiae cell wall, and its multiple biological activities are essential for immune regulation. However, the effect of B-glucan on the intestinal immune response during colitis-associated colorectal cancer (CAC) is unclear. CAC induced by AOM [azoxmehtane]/DSS [dextran sodium sulfate]-had fewer tumors than untreated mice after oral B-glucan and dextran sodium sulfate [DSS] because of increased antitumor dendritic cells (DCs) in the tumor microenvironment, resulting in more CD8:T cells and the production of related cytokines.

…These data suggest that B-glucan improves experimental intestinal inflammation and delays the development of CAC. Therefore B-glucan is feasible for treating chronic colitis and CAC [colitis-associated colorectal cancer] in clinical practice.”

Inflammation – Carrier – Gene: WJ Jing, Rong MZ, Zhang MQ, Wong WL, “Preparation of a water soluble aminated B-1,3-D-glucan for gene carrier: The in vitro study of the anti-inflammatory activity and transfection efficiency,” J Biomed Mater Res A, PMID: 34110080, https://doi.org/10.1002/jbm.a.37244, Jun 10 2021. Quote: “B-1,3-D-glucan has been reported to have a series of bioactivities including antitumor, antimicrobial, anti-inflammatory and antioxidative effects; …AG [aminated glucan] shows no obvious cytotoxicity …and it exerts potent anti-inflammatory effect …posses[ing] an appropriate particle size ranged from 192.8 to 118.4 nm [nanometers = 0.1 to 0.2 microns]. …These results indicate that AG [aminated glucan] is a potential candidate for DNA delivery system due to its potent anti-inflammatory effect and high transfection efficiency.” Note: “Transfection” commonly refers to the introduction of nucleic acids into animal cells.

Inflammation – Intestinal: Rahman S, Davids M, et al, “Dietary Curdlan [particulate beta glucan] Enhances Bifidobacteria and Reduces Intestinal Inflammation in Mice,” Nutrients, 13(4):1305, PMID: 33920960, https://doi.org/103390/nu13041305 , April 15 2021. “Quote: “While humans and mice lack the required enzymes to digest B-glucans, certain intestinal microbes can digest B-glucans, triggering gut Microbial changes. Curdlan, a particulate B-glucan …induced a global change in the microbial composition of the healthy intestinal microbiota from a human. …curdlan [particulate beta glucan] induces microbiota changes that could reduce intestinal inflammation.”

Inflammation – TNF Alpha – Pancreatitis : Koliakos NN, Renieris G, Sotiropoulos D, et al, “Immunomodulation Through Beta-D-glucan in Chemically-Induced Necrotizing Pancreatitis,” J Surg Res, 261:74-84, PMID: 33421796, https://doi.org/10.1016/j.jss.2020.12.020 , Jan 6, 2021. Quote: “21 -d survival was prolonged after pretreatment or treatment with B-D-glucan; …Bacterial load was lower after pretreatment or treatment with B-D-glucan … . Tumor necrosis factor alpha [TNF alpha] production from stimulated peripheral blood mononuclear cells was significantly decreased, whereas interleukin 10 production remained unaltered after pretreatment or treatment with B-D-glucan. Conclusion: B-D-glucan reduces mortality of experimental pancreatitis in vivo. This is mediated through attenuation of cytokine production and prevention of bacterial translocation.”

Inflammation – Anti-inflammatory Adjuvant Carrier: Salaminova P, Cerna L, Majerska M, Smejkal K, “Incorporating natural anti-inflammatory compounds into yeast glucan particles increases their bioactivity in vitro,” Int J Biol Macromol, S041-8130(2)35274-0, PMID 33340625, https://doi.org/10.1016/j.ijbiomac.2020.12.107, Dec 16 2020. Quote: “Yeast glucan particles (GPs) are promising agents for the delivery of biologically active compounds as drugs. This study aimed to determine how incorporating artemisinin, ellagic acid, (-)-epigallocatechin gallate, morusin, or trans-resveratrol into GPs affects their anti-inflammatory and anti-oxidant potential in vitro. …Natural compounds incorporated into yeast GPs showed greater anti-inflammatory potential in vitro …as demonstrated by their inhibition of the activity of transcription factors NF-kAB/AP-1 and the secretion of the pro-inflammatory cytokine TNF-alpha.”

Inflammation: Human Double Blind Trial -Intense Exercise: Zabriskie HA, Blumkatis JC, et al, “Yeast Beta-Glucan Supplementation Downregulates Markers of Systemic Inflammation After Heated Treadmill Exercise,” Nutrients, 12((4):E1144; PMID 32325856, https://doi.org/10.3390/nu1204144, Apr 19 2020. Quote: “Aerobic exercise and thermal stress instigate robust challenges to the immune system. …The purpose of this study was to identify the impact of yeast beta-glucan (Saccharomyces cerevisiae) supplementation on exercise-induced muscle damage and inflammation. In conclusion, a 13-day prophylactic [advance] period of supplementation with 250 mg of yeast derived beta-glucans invoked favorable changes in cytokine markers of inflammation after completing a prolonged bout of heated treadmill exercise.”

Inflammation -Gut: Gudi R, Suber J, et al, “Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice,” J Nutr, https://doi.org/10.1093/jn/nxz328, PMID: 31879786, Dec 27 2019. Quote: “The aim of this study was to investigate the impact of orally administered highly purified, yeast-derived Beta Glucans (YBG; B-1,3/1,6-d glucan). Studies using B6 mice show that dietary Beta Glucans are beneficial for promoting intestinal health when the gut microbiota is intact.”

Inflammation: Sugita P, Sargowo D, “Abstract 366: Beta-1,3/1,6-D-Glucan Chemical Structure Characterization of Indonesian Ganoderma lucidum Mycelium Extract,” Artheriosclerosis, Thrombosis and Vascular Biology (ATVB) Vol 39, Issue Suppl 1, July 19, 2019. Quote: “B-1,3/1,6-D-Glucan may act as an anti-inflammatory and oxidative stress suppressor which may result in the repair of cardiomyocytes and prevent ischemia.”

Inflammation – Upper Respiratory Tract Infection – Double blind Human Clinical Study / Anti-inflammatory: Dharsono T, Rudnicka K, Wilhelm M, Schoen C, “Effects of Yeast (1,3)-(1,6-Beta-Glucan on Severity of Upper Respiratory Tract Infections (URTIs): A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Subjects,” J Am Coll Nutr, Epub, PMID: 30198828, https://doi.org/10.1080/07315724.2018.1478339 . Sept 2018. Quote, “Subjects supplementing with yeast beta-glucan benefit by a reduced severity of physical URTI symptoms during the first week of an episode,…Furthermore, accompanying benefits in terms of blood pressure and mood were identified. Altogether, yeast beta-glucan supports the immune function to defend against pathogens in the upper respiratory tract. In the study of Mosikanon et al, the increase of IL-10 [by beta glucan] was associated with a significant reduction of pro-inflammatory cytokines IL-6 and tumor necrosis factor (TNF)-a. …beta glucan administration may train the monocytes to react more quickly and more efficiently by the robust production of anti-inflammatory cytokines that facilitate the blockage of the inflammatory process and the severity of the symptoms.”

Inflammation – Suppression / Anti-inflammatory – Cao Y, Sun Y, Zou S, Duan B, Sun M, Xu X, “Yeast B-Glucan Suppresses the Chronic Inflammation and Improves the Microenvironment in Adipose Tissues of ob/ob Mice,” J Agric Food Chem, https://doi.org/10.1021/acs.jafc.7b04921, PMID: 29285925, Jan *, 2018. Quote: “…yeast B-1,3-glucan (BYG)…decreased pro-inflammatory modulators of TNF-α, IL6, IL-1B, CCL2 and SAA3, and increased anti-inflammatory factors …Remarkably, BYG decreased the degree of adipose tissue macrophages (ATMs) infiltration, BYG increased the protective Th2 cell regulator GATA3 and decreased immunosuppressors IL-10 and IL-1ra, suggesting the BYG elicited inflammation inhibition via stimulating immune responses. …BYG increased the gut microbiota…and improved the microenvironment of visceral adipose tissues (VATS) through decreasing fibrosis [thickening of connective tissue] and angiogenesis [development of new blood vessels]. These findings suggest that BYG has anti-inflammatory effect in diabetic mice, which can be used as a food component and/or therapeutic agent for diabetes.”

Inflammation – Periodontal Disease – Diabetes: Silva VO, Lobato RV, et al, “Effects of B-Glucans Ingestion on Alveolar Bone Loss, Intestinal Morphology, Systemic Inflammatory Profile, and Pancreatic B-Cell Function in Rats with Periodontitis and Diabetes,” Nutrients, 14;9(9). PMID 28906456, Sept 14, 2017, Quote: “The study aimed to evaluate the effects of B-glucan ingestion (Saccharomyces cerevisiae) on the plasmatic levels of tumor necrosis factor-a (TNF-a0 and interleukin-10 (IL-10), alveolar bone loss, and pancreatic B-cell function (HOMA_BF) in diabetic rats with periodontal disease (PD). …B-glucan ingestion reduced the systemic inflammatory profile, prevented alveolar bone loss, and improved B-cell function in diabetic animals.”

Inflammation – Obesity: Mosikanon K, Arthan D, et al, “Yeast B-Glucan Modulates Inflammation and Waist Circumference in Overweight and Obese Subjects,” J Diet Suppl, PMID 27715351, August 11:1-13 2016: Quote: “A randomized, double blinded, placebo-controlled, clinical trial design enrolled 44 overweight/obese participants with body mass index ≥23 kg/m2. This study investigated the potential effect of yeast β-glucan on inflammatory cytokines in overweight/obese people….Increased inflammation occurs with excessive adiposity [fat] and yeast β-glucan modulates immune responses. …β-glucan increased interleukin-10 (IL-10), an anti-inflammatory cytokine, by 23.97% from baseline at week two (p < 0.001) and 31.12% at week six….

β-glucan reduced pro-inflammatory cytokines IL-6 at week six (p = 0.005) and tumor necrosis factor-α at week two (p = 0.037) compared with controls…. Supplementation of yeast β-glucan for six weeks modulated pro-cytokines that accelerate overweight/obese comorbidities [multiple negative health issues] and reduced blood pressure as well as waist circumference, the strong risk factors for cardiovascular disease, in overweight/obese subjects. Thus, β-glucan might have the potential to decrease comorbid [multiple concurrent negative health issues] conditions associated with overweight/ obesity.”

Inflammation – Beta Glucan; Randomized, Double Blind, Placebo Controlled Study: Lee JG, Kim YS, Lee YJ, et al, “Effect of Immune-enhancing Enteral Nutrition Enriched with or without Beta-Glucan on Immunomodulation in Critically III Patients,” Nutrients, 8(6), 336; https://www.doi.org/10.3390/nu8060336, Jun 2 2016. Quote: “This study showed beneficial effects of a combination treatment of B-glucan and IMHP [immune-modulating nutrients] on NK cell activity. Additionally, strong correlations among changes in NK cell activity, PBMC IL-12 and hs-CRP suggested that B-glucan could be an attractive candidate for stimulating protective immunity without enhanced inflammation.”

Inflammation: Raa J, “Immune modulation b non-digestible and non-absorbable beta-1,3/1,6-glucan,” Micro Edo in Heal & Disease, Vol 26:1, Issue s3, DOI: 103402/mehd.v25.27824, May 29 2015. Quote: “Due to their ability to enhance infection defense mechanisms and simultaneously down-regulate inflammations, beta-1,3/1,6-glucan is very promising as an alternative to the mainstream use of immunosuppressive drugs to treat inflammatory diseases, for instance, IBD.

…Oral administration of beta-1,3/1,6 glucan exhibits intestinal anti-inflammatory activity, and they suggest that beta-1,3/1,6 glucan may be effective for the treatment of gut inflammation, including Inflammatory bowel disease (IBD). Beta-1,3/1,6 glucans counteract not only LPS-induced inflammations but also the inflammation elicited by influenza virus. The ability of beta-1,3/1,6-glucan to suppress inflammatory response has been tested also in humans scheduled for coronary artery bypass grafting. Pretreatment for 5 days with oral particulate beta1-,e/1,6 glucan caused significantly lowered creatine kinase isozyme and cardiac troponin levels the first day of pot operation, and it was concluded that beta-1,3/1,6 glucan pretreatment is safe and may protect against ischemia reperfusion injury following CABG [Coronary artery bypass grafting]. Note: glycans are polysaccharides including yeast glucans containing other sugars than glucose.

Inflammation: Ibin D, Chengyuan L, et al. “An insight into anti-inflammatory effects of fungal beta-glucans,” Trends in Food Sci & Tech, Vol 41 Issue 1, pg 49-59, Jan 2015. Quote: “B-Glucans from fungi exhibit a broad spectrum of biological activities including anti-tumor, immune-modulating and anti-inflammatory properties. The anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide (NO), interleukins (ILS) tumor necrosis factor alpha (TNF)-α, interferon gamma (INF)-y as well as non-cytokine mediator, prostaglandin E2 (PGE2.”

Inflammation – Anti-Inflammatory: Steir H, Ebbeskotte V, Gruenwald J, “Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan,” Nutr J; 13;38, PMID 24774968, https://doi.org/10.1186/1475-2891-13-38 , Apr 28, 2014. Quote: “Indeed, yeast β-glucan consumption had an impact on immune function, as shown by an increase of both circulating levels and adipose tissue messenger RNA (mRNA) expression of the anti-inflammatory cytokine IL-10. Insulin sensitivity as well as circulating levels and mRNA expression of pro-inflammatory cytokines were, however, unaffected. The results indicate that intake of particulated yeast β-glucans also has anti-inflammatory properties. …These studies provide evidence on the potential immunmodulatory effects of yeast B-glucans. On the one hand, the substances eliit/amplify (activate) the immune reaction as shown in the prevention of infections; on the other hand, they are capable of reducing the inflammatory reaction by inducing anti-inflammatory processes.”

Inflamation-Sepsis: Abdulkadir B, Mustafa K, et al, “Beta-Glucan Attenuates Inflammatory Cytokine Release and Prevents Acute Lung Injury in an Experimental Model of Septis,” Shock, Vol 27(4) p397-401, DOI: 10.1097/01.shk.0000245030.24235.f1, Apr 2007. Quote: “In this study we investigated the putative protective role of B-glucan against sepsis-induced lung injury. …The present study demonstrates that B-glucan, a clinically relevant nonspecific immunomodulator, can significantly attenuate the expression of proinflammatory cytokines and systemic inflammation in rat after sepsis. We have also shown that B-glucan can affect the lethality and occurrence of acute lung injury as measured through end-organ histological damage in response to sepsis. …

We have previously shown the beneficial effects of B-glucan such as decreased weight loss, anastomotic leakage, and mortality in the setting of peritonitis. These findings, therefore, suggest that immunomodulation with B-glucan mediates the inhibition of the cytokine response, leading to a regression of neutrophilic lung inflammation. We propose that B-glucan might be used as a therapeutic agent in the treatment of inflammatory lung injury related to sepsis.”

Inflamation: Luhm J, Langenkamp U, et al, “Beta-(1–>3)-D-glucan modulates DNA binding of nuclear factors kappaB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1beta/IL-1 receptor antagonist ratio,” BMC Immunol, 22;7:5, DOI: 10.1186/1471-2172-7-5, PMID: 16553947, Mar 2006. Quote: “Beta-1–>3-D glucans represent a pathogen-associated molecular pattern and are able to modify biological responses. …Thus, beta-1–>3-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction.”

Inflamation: Down Regulatory also : Hunter, KW Jr, DuPre S, Redelman D, “Microparticulate Beta-Glucan Upregulates the Expression of B7.1, B7.2, B7-H1 [also known as PD-L1] , but Not B7-DC on Cultured Murine Peritoneal Macrophages,” Immunol Let 93(1), 71-8, PMID: 15134902, https://doi.org/10:1016/j.imlet.2004.02.006, Apr 30 2004. Quote: “Beta-1,3-(D)-glucan from a variety of biological sources has been shown to enhance both humoral and cellular immune responses to a variety of antigens, infectious agents, and tumors. …This study has demonstrated that a microparticulate form of beta-glucan can enhance B7 co-stimulatory molecule expression on macrophages, thereby enabling these antigen-presenting cells to deliver the second signal to T-lymphocytes that express CD28 [glycoprotein cytotoxic T-cells]. …MG [Microparticulate beta-glucan] upregulated B7.2 mRNA expression and enhanced the surface membrane expression of B 7.2 glycoprotein. …In addition, because MG also induces the expression of B7-H1 [also known as PD-L1], it may enable macrophages to provide a concomitant downregulatory signal [anti-inflammatory] to T-lymphocytes expressing PD-1 or related receptors “

Inflammatory Bowel Disease: Veraperumal SV, Qiu HM, et al, “Restitution of epithelial cells during intestinal mucosal wound healing: the effect of a polysaccharide from the scleroium of lignosus rhinocerotis (Cooke) Ryvarden,” J Ethnopharmacol, 114024, PMID: 33727110, https://doi.org/10.1016/j.jep.2021.114024 , Mar 13 2021. Quote: “The present study reveals that the prepared B-glucan accelerates intestinal epithelial cell proliferation and migration… . Hence, B-glucan can be employed as a prospective therapeutic agent for the treatment of diseases associated with gastrointestinal mucosal damage, such as peptic ulcers and inflammatory bowel disease.”

Inflammatory Bowel Disease (IBD): Spagnuoto R, Cosco C et al, “Beta-glucan, inositol and digestive enzymes improve quality of life of patients with inflammatory bowel disease and irritable bowel syndrome.” Eur Rev Med Pharmacol Sci, Supply:102-107, PMID: 28724171, June 21, 2017. Quote: “We have shown that supplementation with a mixture of beta-glucan, inositol and digestive enzymes reduces bloating, flatulence and abdominal pain, improving the overall clinical condition of IBD-IBS patients.”

Influenza; See also “flu” and “colds” and “Upper Respiratory Infections

Influenza: Respiratory Tract Infection: Shokri-Mashhadi N, Kazemi M, et al, “Effects of select dietary supplements on the prevention and treatment of viral respiratory tract infections [RTI]: a systematic review of randomized controlled trials,” Expert Review of Respiratory Medicine, 15:6, 805-82, https://doi.org/10.1080/17476348.2021.1918546 , April 26, 2021. Quote: “Yeast beta-glucan supplementation may be associated with decreased RTIs [respiratory tract infections] symptoms such as the number of days with the common cold or flu symptoms.”

Influenza: β-glucans – Jin Y, et al, “B-glucans potential immunoadjuvants: A review on the adjuvanticity, structure-activity relationship and receptor recognition properties.” Vaccine, 36(35):5235-5244. doi, Aug 23 2018. Quote: “In recent years, B-glucans have been studied as adjuvants in anti-infection vaccines as well as immunomodulators in anti-cancer immunotherapy. B-glucans can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines.”

Influenza: Nakashima A, Suuki K, et al, “Oral administration of Euglena gracilis Z and its carbohydrate storage substance [B-1,3-glucan] provides survival protection against influenza virus infection in mice.” Biochem Biophys Res Commun, 494(1-2:379-383, PMID: 28974421, Dec 9 2017. Quote: “Our data therefore reveals a novel immunoregulatory role of the Euglena gracilis Z and paramylon [B-1,3-glucan] which provides protection against influenza virus infection.”

Influenza Vaccine: Wang M, Zhang L, et al, “Improvement of immune responnses to influenza vaccine (H5N1) by sulfated yeast beta glucan,” Int J Biol Macromol, 93(Pt A):203-207, PMID: 27339320, Dec 2016. Quote: …the adjuvant activity of sulfated glucan from saccharomyces cerevisiae (sGSC) was investigated. …The results showed that sGSC could significantly enhance lymphocyte proliferation, effectively increase the percentage of CD4 T cells, decrease the percentage of CD8 T cells, and elevate the CD4/CD8 ratio; enhance the Il antibody titre, and promote the production of IL-2, INF-y, IL-4 and IL-6 at medium level. These results indicated that sulfated glucan showed an excellent adjuvant effect on H5N1 vaccine in a mouse model. Therefore, sGSC (sulfated glucan from saccharomyces cerevisiae) could be used as an effective immune adjuvant for an inactivated H5N1 vaccine.”

Influenza: Vetvicka V, Vetvickova J, “Glucan supplementation enhances the immune response against an influenza challenge in mice.” Ann Transl Med, 3(2):22 PMID 25738142, Feb 2015. Quote: “…we focused on possible effects of a…glucan formulation on immunosuppression caused by influenza infection. We found that a 2-week oral feeding with glucan mixture significantly reduced the effects of influenza infection in total mortality. Our study was focused on phagocytosis, cytokine levels, antibody response and cytotoxicity assay. …Based on our data, we concluded that these effects are caused by [beta glucan] stimulation of both cellular and humoral immune reaction resulting in lower viral load.”

Influenza/Colds: McFarlin BK, Carpenter KC, Davidson T, “Baker’s yeast beta glucan supplementation increases salivary IgA [immunoglobulin] and decreases cold/flu symptomatic days after intense exercise,” J Diet Suppl 10(3):171-83, PMID: 23927572. Sept 2013. Quote: “BG [beta glucan] was associated with a 37% reduction in the number of cold/flu symptom days postmarathon compared to placebo (p = .026). In E2, BG was associated with a 32% increase in salivary IgA [immunoglobulin A].” Note: Immunoglobulin A is an antibody that plays a critical role in immune function in the mucous membranes and is suggested often by physicians as an influenza/cold deterrent due to immune response enhancement.

Influenza: Wang M, Zhang L, et al, “Improvement of immune responses to influenza vaccine (H5N1) by sulfated yeast beta-glucan,” Int J Biol Macromol, (Pt A):203-207. PMID: 27339320, Jun 23 2016. Quote: “These results indicated that sulfated glucan [from saccharomyces cerevisiae – sGSC] showed an excellent adjuvant effect on H5N1 vaccine in a mouse model. Therefore, sGSC could be used as an effective immune adjuvant for an inactivated H5N1 vaccine.”

Influenza-Macrophage Activation Beta Glucan: Raa J, “Immune modulation by non-digestible and non-absorbable beta-1,3/1,6-glucan,” Microbial Ecology in Health & Disease, Vol 26:1, Issue s3, https://doi.org/103402/mehd.v25.27824, May 29 2015. Quote: “More than 30 years ago, Seljelid and co-workers screened a large number of glucans and glycans …for their macrophage-activating ability in vitro, and found that a particulate beta-1,3/1,6-glucan prepared from baker’s yeast was the most active. Products with only one single glucose molecule in the side chain, as in most mushroom beta-1,3/1,6-glucans, have lower macrophage activating activity than yeast cell-wall beta 1,3/1,6 glucan. …Due to their ability to enhance infection defense mechanisms and simultaneously down-regulate inflammations, beta-1,3/1,6-glucan is very promising as an alternative to the mainstream use of immunosuppressive drugs to treat inflammatory diseases, for instance, IBD.

Influenza/Colds-Human Studies: Talbott SM, Talbot JA, “Baker’s yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women.” J Am Col Nutr, 31(4):295-300, PMID 23378458, Aug 2012. Quote: “Several studies have shown a baker’s yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. ...These data show the daily dietary supplementation with a beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.”

Influenza/Colds-Human Study: Feldman SS, Kalman DS, Mayers A, Kohrman HM, Clemens R, Krieger DR, “Randomized Phase II Clinical Trials of Wellmune for Immune Support During Cold and Flu Season,” Journal of Applied Research: 9:30-42; Miami Research Associates, USC School of Pharmacy, July 16, 2009. Quote: “This pilot trial examined whether beta-glucan derived from Saccharomyces cerevisiae can favorably decrease the risk of or symptomology associated with upper respiratory illness. Forty healthy adult subjects (18-65 years of age) were enrolled in a 12-week randomized, double-blind, placebo-controlled parallel-group trial conducted during cold/flu season. The treatment compared Wellmune WGP gluco polysaccharide (beta glucan) (500 mg/d) vs a placebo (500 mg rice flour). Cold/flu symptoms were evaluated by medical staff … . There were no significant differences in the incidence of symptomatic respiratory infections (SRIs) among the study groups. However, none of subjects in the WGP group missed work or school due to colds, while …the placebo group missed an average of 1.38 days. Quality of Life, assessed by the Physical Component Summary score, improved significantly in the WPG group vs the placebo group after 90 days … . The WGP group had a significantly lower average fever score that the placebo group … . No adverse events were detected and no safety concerns were presented. This preliminary study suggests 1,3-1,6 beta-glucan from Saccharomyces cerevisiae may modulate the immune system and reduce some risks associated with upper respiratory influenza infections.”

Influenza: Akramlene D, Konddrotas A, et al, “Effects of B-glucans on the immune system,” Medicina (Kaunas), 43(8), Kaunas U of Med, Lithuania, Aug 6 2007. Quote: “It has been common knowledge in the scientific community that B-glucan is the most known powerful immune stimulant and a very powerful antagonist to both benign and malignant tumors; it lowers cholesterol and triglyceride level, normalizes blood sugar level, heals and rejuvenates the skin and has various other benefits. …B-Glucan itself can elicit broad anti-infective effects. Staphylococcus aureus, Escherichia coli, Candida albicans, Pneumocystis carinii, Listeria monocytogenes, Leishmania donovani, Influenza virus are microorganisms, against which a protective effect of B-glucan has been established.”

Influenza Virus/Colds: Jung K, et al, “Antiviral effect of Saccharomyces cerevisiae beta-glucan to swine influenza virus by increased production of interferon-gamma and nitric oxide,” J Vet Med B Infect Dis Vet Public Health 51(2):72-6, PMID: 15030604, Mar 2004. Quote: “Saccharomyces cerevisiae beta-glucan reduced the pulmonary lesion score and viral replication rate in SIV [swine influenza virus] -infected pigs. These findings support the potential application of beta-glucan as prophylactic/treatment agent in influenza virus infection.” Note: prophylactic treatment refers to a preventative agent. Interferon-gamma is a protective antiviral.

Influenza Vaccine Adjuvant: Wang M, Yang R, et al, “Improvement of immune response to influenza vaccine (H5N1) by sulfated yeast beta glucan,” Int J Biol Macromol, 93(Pt A) 203-207. PubMed 27339320. June 23, 2016. Quote: “The adjuvant activity of … glucan from saccharomyces cerevisiae (GSC) was researched…with inactivated H5N1 vaccine. The research showed that GSC could significantly enhance lymphocyte [white blood cell] proliferation, effectively increase the percentage of CD4*T Cells, decrease the percentage of CD8*T Cells and elevate the CD4/CD8 ratio, enhance the Hl antibody titer, and promote the production of IL-2, INF-y, IL4 and IL-6 at medium level. …GSC could be used as an effective immune adjuvant for an inactivated H5N1 vaccine.” Note: GSC is beta 1,3/1,6 glucan. CD4 and CD8 are T Helper Cells. IL2-cytokine white immune cell regulator. IL4-induces differentiation to Th2 cells.

Injury (from irradiation): Daniel E Cramer, Daniel J Allendorf, Jarek T Baran, Richard Hansen, Jose Marroquin, Bing Li, Janina Ratajczak, Mariusz Z Ratajczak, and Jun Yan; “Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury;” Blood; DOI 10.1182. Tumor Immunobiology Program and Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. Sept 2005. Quote: “…Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM [bone marrow] stroma [cell framework]. … Taken together, these observations suggest a novel role for C, CR3, and Beta glucan in the restoration of hematopoiesis [cell formation] following injury.” NOTE: Mice were treated for 12 days with beta glucan and exposed to a sublethal dose of radiation. The beta glucan treated animals had approximately 40 percent more cell formation units in the spleen than untreated mice. When beta glucan was given orally, survival of animals receiving a lethal dose of radiation after stem cell transplantation was significantly enhanced. Forty days following radiation exposure, approximately 30 percent of mice treated with beta glucan survived compared with only 3 percent of untreated animals.

Injury: See Thermal Injury also.

Insulitis: Kida K, Inoue T, Kaino Y, Goto Y, Ikeuchi M, Ito T, Matsuda H, Elliott RB. “An immunopotentiator of beta-1,6;1,3 D-glucan prevents diabetes and insulitis in BB rats.” Dept of Pediatrics, Ehime U Sch of Med, Japan; Diabetes Res Clin Pract 17(2):75-9, PMID 1425150; Aug 1992. Quote: “The intravenous administration of 1 mg kg- 1 week- of beta-1,6;1,3 D-glucan from the age of 4 weeks decreased the cumulative incidence of diabetes from 43.3% to 6.7% and also incidence of insulitis from 82.4% to 26.3% at the age of 20 weeks. …These data indicate that immunopotentiators [beta-1,6;1,3 D-glucan] could modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes in BB rats.”

Innate Immune Response

Note: Research under this “Innate Immune Response” category does not all contain beta glucan involvement**, but are the initial studies and more recognizing the importance of the immune system innate immune response as the first line of defense and the now established importance of beta 1,3/1,6 glucan in support of that first line of defense.

Innate Immune Response – Beta Glucan – Phagocytosis: Zhang Y, Liu X, Zhao J, et al, “The phagocytic receptors of B-glucan,” Int J or Biological Macromolecules, Vol 205, pp40-441, PMID: 35202631, https://doi.org/10.1016/j.ifbiomac.2022.02.111 , Feb 23 2022. Quote: “Phagocytosis is a cellular process maintaining tissue balance and plays an essential role in initiating the innate immune response. These receptors …also bridge the gap between extracellular and intracellular communication, leading to signal transduction and production of inflammatory mediators, which are crucial for clearing the invading pathogens and maintaining cell homeostasis. ..B-glucan…By binding to specific receptors on immune cells and activating intracellular signal transduction pathways, causes phagocytosis and promotes the release of cytokines.”

Innate Immune Response – Beta Glucan: Castro FM, Calder PC, Roche HM, “B-1,3/1,6-glucans and Immunity: State of the Art and Future Directions,” Mol Nutr Food Res, 65(1):e1901071, https://doi.org/10.1002/mnfr.201901071, (wellm) PMID: 32223047, Jan 2021. Quote: “The immune response is composed of innate and adaptive components. The initial responder to pathogens is the innate component, comprised mainly of phagocytic cells (e.g., neutrophils, monocytes, macrophages, and dendritic cells) able to engulf and kill pathogens. After phagocytosing and digesting pathogens and then processing pathogen‐derived antigens, innate immune cells release inflammatory mediators and cytokines, and present the processed antigen to T helper cells and B lymphocytes, leading to the development of the more specific adaptive immune response.

The T cells and B cells are responsible for the antigen‐specific recognition and destruction of pathogens. Traditionally, the classical adaptive response was attributed to T and B cells able to express different receptors for maximal specificity based on the antigen being presented, while the innate response was understood to rely on receptors only able to recognize highly conserved microbial structures. More recently, it is evident that innate cells have the ability to modify responses by pattern recognition, leading to the concept of innate immune memory or innate immune training.

The main challenge for the innate immune system is to differentiate self or benign from pathogenic antigens. Evolution’s ingenious solution has been to identify microbe‐ or pathogen‐associated molecular patterns (MAMPs or PAMPs), which are different motifs present in invading microorganisms that are lacking in higher eukaryotes. During the early phase of the immune response, MAMPs are recognized by pattern recognition receptors (PRRs) and complement binding (e.g., dectin‐1 and complement receptor 3 for β‐glucan signaling), which prompt a rapid detection and control of pathogen invasion via initiation of an innate immune response. …Overall, no adverse events were detected, and no major safety concerns were presented in response to any of the selected intervention studies. “

Innate Immune Response*: Rusek P, Wala M, et al, “Infectious Agents as Stimuli of Trained Innate Immunity,” Int J Mol Sci, 19(2):456, https://doi.org/10.3390/ijms19020456, PMID 29401667, Feb 3 2018. Quote: “When the host organism encounters an infectious agent, its immune response is triggered. This mechanism consists of three steps: recognition of a pathogen, response to its activity (immune reaction), and eradication of pathogen from the host organism. Immunity can be divided into innate (non-specific) and acquired/adaptive ([humoral-] specific) responses-both of them are manifested by cellular and humoral mechanisms.

Innate Immune Response and Beta Glucan: Raa J, “Immune modulation by non-digestible and non-absorbable beta-1,3/1,6-glucan,” Microbial Ecology in Health & Disease, Vol 26:1, Issue s3, https://doi.org/10.3402/mehd.v26.27824, May 29 2015. Quote: “White blood cells with beta-1,3/1,6 glucan and its specific receptors constitute the backbone of the body’s innate immune system, which is the first line of defense against most infections.”

Innate Immune Response – Fungal Defense – Dectin-1 Immune Cell Receptor: Brown GD, Gordon S, Herre J, Willment JA, “The role of Dectin-1 in antifungal immunity,” Crit Rev Immunol, 24(3):193-203, PMID 15482254, 2004. Quote: “Dectin-1 [C-type lectin-like receptor] is expressed on phagocytic cells, including macrophages and neutrophils, and mediates both the internalization and cellular responses to beta-glucan… . Dectin-1 can recognize and respond to live fungal pathogens…having a key role in the innate responses to these pathogens.“

Innate Immune Response *: Lolis E, Bucala R, “Therapeutic approaches to innate immunity: severe sepsis and septic shock,” Nat Rev Drug Discov, 2(8):635-645, PMID: 12904813, https://doi.org/10.1038/nrd1153 , Aug 1 2003. Quote: “Severe sepsis leading to shock is the principal cause of death in non-cardiac intensive care units. This condition develops because of a dysregulation in host responses, such that the mechanisms initially recruited to fight infection produce life-threatening tissue damage and death. Recent advances in our understanding of innate immunity, and the interaction between the inflammatory and the haemostatic cascades, are affording new opportunities for therapeutic development.” Note: The process of hemostasis protects and maintains the balance between blood loss and thrombotic events.

Innate Immune Response *: Wakimoto H, Johnson PR, et al, “Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells,” Gene Ther, 10(11):983-90, PMID: 12756419, https://doi.org/10.1038/sj.gt.3302038 , Jun 2003. Quote: “The first line of defense against wild-type HSV1 [herpes simplex virus 1] infection in both naive and immunized individuals is provided by innate humoral (complement, cytokines, chemokines) and cellular (macrophages, neutrophils, NK cells, gammadelta T cells, and interferon-producing cells) responses. These orchestrate the lysis of virions and virus-infected cells as well as provide a link to effective adaptive immunity.” Note: “lysis” refers to the breakdown of a cell caused by damage to its (outer) membrane.

Innate Immune Response *: Sfondrini L, Balsair A, et al, “Innate immunity in breast carcinoma,” Endocr Relat Cancer, 10(2):301-308, PMID: 12790791, https://doi.org/10.1677/erc.0.0100301, Jun 2003. Quote: “The experimental findings raise the possibility of successful anti-tumor management through stimulation of innate immunity … “

Innate Immune Response *: Bassett C, Holton J, et al, “Innate immunity and pathogen-host interaction,” Vaccine, 1:21 Suppl 2:S12-23, PMID: 12763678, https://doi.org/10.1016/so264-410x(-3)00195-6 , Jun 2003. Quote: “We focus on the innate immune system in the mucosa, which manages to deal with invading pathogens, the mechanisms that organisms have evolved in order to circumvent this primary defensive barrier and finally, potential therapeutic manipulation of the innate immune system…”

Innate Immune Response *: Beyan H, Buckley IR, et al, “A role for innate immunity in type 1 diabetes?,” Diabetes Metab Res Rev, 19(2):89-100, PMID: 12673777, https://doi.org/10.102/dmrr.341, Mar-Apr 2003. Quote: ” Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders.”

Innate Immune Response-Fungal Infections: Brown G D, Gordon Siamon; “Fungal B-Glucans and Mammalian Immunity.” Sir William Dunn Sch of Pathology, U of Oxford, UK, Immunity, Vol19, 311-316, 2003. Quote: “B-Glucans are structural cell wall polymers of many fungi which possesses immunomodulatory activities. …The innate immune response is essential for the control of fungal infections, and there is increasing evidence that B-glucans are involved in initiating many aspects of this response. The recognition of fungal pathogens occurs through both opsonic (mainly complement) and nonopsonic mechanisms, and as conserved structural components, B-glucans…play an important role in the non-opsonic recognition of these [fungal] pathogens.

Innate Immune Response *: Levy JA, “The importance of the innate immune system in controlling HIV infection and disease,” Trens Immunol, 22(6):312-316, PMID: 113377290, https://doi.org/10.1016/s1471-4906(01)01925-1 , Jun 2001. Quote: “The innate immune system is the first line of defense against invading pathogens and is particularly important in warding off bacterial and viral infections presenting at the mucosal cell surface.”

Innate Immune Response*: Gura T, et al, “Ancient System Gets New Respect,” Science Vol 291, Issue 5511, pp 2068-2071, https://doi.org/10.1126/science.291.5511.2068, Mar 16, 2001. Quote, “Unlike the so-called acquired immune system, with its disease-fighting cells and antibodies, innate immunity depends on peptides and small proteins to fight off dangerous microbes.”

Innate Immune Response: Hunter KW, Jordan FM, Gault RA, “The Use of B 1,3-Glucan Containing Compositions to Potentiate Immune Responses by Upregulating the Expression of Costimulatory Molecules,” U.S. Patent Application 09/707,582, Nov 3 2000. Quote: “…glucan-containing compositions potentiate immune responses by causing the activation of macrophages. When B-glucan-containing compositions interact with the cell surface glucan receptor, [dectin 1, CR3,] the macrophage is activated and becomes capable of direct and indirect killing of the invading pathogen or tumor.…macrophage activation is certainly important for innate immunity through the enhanced destruction of pathogenic microorganisms and tumors, … .There is evidence that beta glucan-containing compositions can potentiate both innate and adaptive immunity, … .”

Innate Immune Response:Bacterial Infections: Wyde, P., “Beta-1,3-glucan activity in mice: intraperitoneal and oral applications.” Baylor College of Medicine Research Report. 1989. Quote: “This demonstration of bactericidal enhancement via oral dosing suggests an application for beta-1,3-glucan as a component in a combined modality with conventional anti-infective agents. Beta glucan, through the stimulation of host defense systems, creates a more supportive environment within the body to assist the primary killing action of the conventional agent.”

Innate Immune Response:Bacterial Infections: Czop, Joyce K., “The Role of Beta.-Glucan Receptors on Blood and Tissue Leukocytes in Phagocytosis and Metabolic Activation”. Pathology and Immunopathology Research; 5:286-296. Harvard Medical School. 1986. Quote: “…the presence of a particulate activator can rapidly initiate assembly and amplification of a host defense system involving humoral and cellular interactions with B-glucans. …Animals pretreated with purified glucan particles are subsequently more resistant to bacterial, viral, fungal, and protozoan challenge, reject antigenically incompatible grafts more rapidly and produce higher titers of serum antibodies to specific antigens. Administration of glucan particles …stimulates…proliferation of macrophages and increases in phagocytic and secretory activities of macrophages. …A cascade of interactions and reactions initiated by macrophage regulatory factors can be envisioned to occur and to eventuate in conversion of the glucan-treated host to an arsenal of defense.”

Interferon

Grandvaux N, tenOever BR, et al, “The interferon antiviral response; from viral invasion to evasion,” PMID: 12015460; https://doi.org/10.1097/00001432-200206000-0000g ,

Interferon: Trained Immunity – Tuberculosis – Beta Glucan: Khan N, Downey J, et al, “M. [Mycobacterium] tuberculosis [Mtb] Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity,” Cell 183(3):752-770, PMID: 33125891, https://doi.org/10.1016/j.cell.2020.09.062 , Oct 29, 2020. Quote: “We have shown that systemic administration of Bacille Calmette-Guerin (BCG) or B-glucan reprograms HSCs [hematopoietic stem cells] in the bone marrow (BM) via a type II interferon (IFN-II) or interleukin-1 response, respectively, which confers protective trained immunity against Mtb. Here we demonstrate that, unlike BCG or B-glucan, Mtb reprograms HSCs via an IFN-I response that suppresses myelopoiesis and impairs development of protective trained immunity to MtB.

Mechanistically, IFN-I signaling dysregulates iron metabolism, depolarizes mitochondrial membrane potential, and induces cell death specifically in myeloid progenitors. Additionally, activation of the IFN-I/iron axis in HSC’s impairs trained immunity to Mtb infection. These results identify an unanticipated immune evasion strategy of Mtb [Mycobacterium tuberculosis] in the BM [bone marrow] that controls the magnitude and intrinsic anti-microbial capacity of innate immunity to infection.”

Interferon – Aspergillus Fungal Defense: Dutta O, Espinosa V, et al, “Dectin-1 Promotes Type I and III Interferon Expression to Support Optimal Antifungal Immunity in the Lung,” Front Cell Infect Microbiol, 10:321, https://doi.org/10.3389/fcimb.2020.00321, PMID: 32733815, Jul 8 2020. Quote: “Pulmonary infections with Aspergillus fumigatus (AF) are a significant cause of invasive fungal disease and lead to high morbidity and mortality in diverse populations throughout the world. …we demonstrate that dectin-1-mediated recognition of B-glucan on the cell wall of the clinically relevant fungal pathogen Aspergillus fumigatus promotes the activation of a protective cascade of type I and III interferon expression [antiviral]. We further demonstrate that exogenous administration of type I and III interferons can rescue inadequate antifungal responses in dectin-1 mice, suggesting the potential therapeutic benefit of these cytokines as activators of antifungal defense in the context of innate defects. …We find that dectin-1-dependent recognition of B-glucan exposure during Af germination induces increased production of type I and III interferons.” Note: “Exogenous” is originating or produced outside a cell, tissue or organism. Note: Dectin-1 is a beta 1,3/1,6 glucan receptor on immune cells.

Interferon – Beta Glucan Human Study: McFarlin BK, Venable AS, Carpenter KC, Henning AL, Ogenstad S, “Oral Supplementation with Baker’s Yeast Beta Glucan Is Associated with Altered Monocytes, T cells and Cytokines following a Bout of Strenuous Exercise,” Front Physiol, 8:786, https://doi.org/10.3389/fphys.2017.00786, (Wellm) PMID: 29104540, Oct 20, 2017. Quote: ” The purpose of this study was to determine if 10 days of oral supplementation with BYBG [Baker’s yeast beta glucan] could modify previously observed suppression of monocytes. BYBG significantly altered total and classic monocyte concentration and expression of CD38, CD80, CD86, TLR2 and TLR4 on monocyte subsets. BYBG also significantly increased CD4+ and CD8 + T cell concentration. …Likewise, BYBG significantly altered serum IFN-y and IL-2, and LPS-stimulated IFN-y, IL-2, IL-4 and IL-7. Taken together these data support the hypothesis that oral BYBG [Baker’s yeast beta glucan] supplementation modulates the expected exercise response for individuals of average fitness. This [supplementation with oral Baker’s yeast beta glucan] may result in a decrease in susceptibility to opportunistic infections after strenuous exercise.”

Interferon – viruses : Volker F, Chattopadhyay, et al, “No Love Lost Between Viruses and Interferons,” Annu Rev Virol,2(1):549-572, PMID: 26958928, https://doi.org/10.1146/annurev-virology-100114-055249, Nov 2015. Quote: “The interferon system protects mammals against virus infections. … In uninfected cells, cell surface receptors recognize the secreted interferons and activate intracellular signaling pathways that induce the expression of interferon-stimulated genes; the proteins encoded by these genes inhibit different stages of virus replication. To avoid extinction, almost all viruses have evolved mechanisms to defend themselves against the interferon system. “

Interferon: Budak F, Goral G, Oral HB, “Saccharomyces Cerevisiae Beta-Glucan Induces Interferon-Gamma Production in Human T Cells Via IL12,” Turk J Immunol, 13:21-26, Vol 13, No. 1, [No PMID or doi] Sep 22, 2008. Quote: “It has been reported that these polymers [Saccharomyces Cerevisiae Beta-Glucans] have a variety of effects on the immune system, including anti-tumor and anti-infective activities against fungal, bacterial, viral, and protozoal Infections. …B-glucan significantly upregulated IFN-y production [Interferon-Gamma]. These data suggest that B-glucan may support anti-tumour and anti-infective immune responses by increasing IL-12-induced IFN-y production in T cells. …it [B-glucan] probably not only induces IL-12 production but also leads to up-regulation of MHC class VII and co-stimulatory molecules (CD80 and CD86) on the surface of antigen presenting cells such as macrophages and dendritic cells.”

Interferon – Influenza Virus: Jung K, et al, “Antiviral effect of Saccharomyces cerevisiae beta-glucan to swine influenza virus by increased production of interferon-gamma and nitric oxide,” J Vet Med B Infect Dis Vet Public Health 51(2):72-6, PMID: 15030604, Mar 2004. Quote: “Saccharomyces cerevisiae beta-glucan reduced the pulmonary lesion score and viral replication rate in SIV [swine influenza virus] -infected pigs. These findings support the potential application of beta-glucan as prophylactic/treatment agent in influenza virus infection.” Note: prophylactic treatment refers to a preventative agent. Interferon-gamma is a protective antiviral.

Interferon – Immune System Down Regulation of Hyperactivity: Pelizon AC, Kaneno R, et al, “Down-modulation of Lymphoproliferation and Interferon-y Production by B-glucan Derived from Saccharomyces cerevisiae,” Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 98(8): 1083-1087, Dec 2003. Quote: “Data demonstrated that both, I.P. administration of particulate B-glucan and in vitro stimulation of splenic cells decreased lymphoproliferation and IFN-y [Interferon y] production induced by concanavalin A. These results suggest that B-glucan can trigger a down-modulatory effect regulating a deleterious immune system hyperactivity in the presence of a strong stimulus.” Note: conclusions translates to “calming effect on a cytokine storm,’ “Lymphoproliferation” is defined as excessive lymphocytes which includes white blood cells B-cells and T-cells.

Interferon: Sen GC, “Viruses and interferons,” Annu Rev Microbiol, 55:255-81, PMID 11544356, https://doi.org/10.1146/annurev.micro.55.1.255 2001. Quote: “The interferon system is the first line of defense against viral infection in mammals. This system is designed to block the spread of virus infection in the body,… Finally, almost all viruses have evoolved mechanisms to evade the interferon system partially blocking…interferon action.”

Interferon: Sakurai T, Ohno N, Yadomae T, “Effects of fungal-glucan and interferon on the secretory functions of murine alveolar macrophags,” J Leukoc Bio, 60:118-24, 1996.

Intestinal Barrier/Wall-Constipation: Chen Z, Lin S, et al, “Effects of Bread Yeast Cell Wall Beta-Glucans on Mice with Loperamide-Induced Constipation,” J Med Food, doi: 10.1089/jmf.2019.4407, PMID: 31536448, Sep 19 2019. Quote: “Constipation is a common gastrointestinal disorder characterized by changes in intestinal habits. Increasing evidence indicates that long-term use of irritant laxatives causes serious side effects. …This study showed that B-glucans can influence the intestinal microbiota to recover intestinal epithelial mechanical barrier. We suggested that B-glucans could be used as an active nutritional supplement to protect the damaged intestinal barrier and help patients who have constipation complications and dysbiosis.” Note: Dysbiosis – Often a gastrointestinal microbial imbalance including small intestinal bacterial or fungal overgrowth.

Intraperitoneal: Beta(1-3)glucan 1.3 Glucan Activity in Mice: Intraperitoneal and Oral Applications. Baylor College of Medicine. Research Summary. 1989.

Inflammatory Bowel Disease – IBD: Spagnuoto R, Cosco C et al, “Beta-glucan, inositol and digestive enzymes improve quality of life of patients with inflammatory bowel disease and irritable bowel syndrome.” Eur Rev Med Pharmacol Sci, Supply:102-107, WMD, PMID: 28724171, June 21, 2017. Quote: “We have shown that supplementation with a mixture of beta-glucan, inositol and digestive enzymes reduces bloating, flatulence and abdominal pain, improving the overall clinical condition of IBD-IBS patients.”

Irritable Bowel Syndrome:- IBS: Ciacci C, Franceschi F, et al, “Effect of beta-glucan, inositol and digestive enzymes in GI symptoms of patients with IBS,” Eur Rev Med Pharmacol Sci, PMID 21796867, Jun 15, 2011. Quote: “Biointol [a mixture of beta-glucan, inositol and digestive enzymes] administration has shown to improve some IBS symptoms, such as bloating, flatulence and abdominal pain, all connected to the presence of gas inside the intestinal lumen.”

Ischemia/reperfusion injury: Samuelson AB, Schrezenmeir j, Knutsen SH, “Effects of orally administered yeast-derived beta-glucans,” Mol Nutr Food Res, 58(1):183-93, PMID 24019098, Jan 2014. Quote: “Yeast-derived beta-glucans are considered immunomodulatory compounds suggested to enhance the defense against infections and exert anticarcinogenic effects. …In human trials, orally administered yeast derived beta-glucans (Y-BG) significantly reduced he incidence of upper respiratory tract infections … . In animal models, oral Y-BG have reduced the incidence of bacterial infections and …enhanced antineoplastic [chemotherapy] agents. …Protective effects toward drug intoxication and ischemia/reperfusion injury [tissue damage when blood supply returns to tissue after period of a lack of oxygen] have also been reported.”

Klebsiella – See also Bacterial and Infections – Bacterial

Kupffer Cells: Deimann W, Fahimi HD, “The Appearance of Transition Forms Between Monocytes and Kupffer Cells in the Liver of Rats Treated with Glucan,” J Exp Med, p883-897, Dept of Anat, U of Heidelberg, Germany.* Apr 1979.

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Learning Impairment-Stress Induced Cognitive Decline: Khan SH, Khan S, et al, “B-1,3-Glucan attenuated chronic unpredictable mild stress induced cognitive impairment in rodents via normalizing corticosterone levels,” Cent Nerv Syst Agents Med Chem, PMID: 32778039, DOI: 10.2174/1871524920666200810142359, Aug 10 2020. Quote: “Chronic stress elevates the cortisol beyond normal levels which affects cognition including learning and memory. … Results of the current study revealed the B-glucan provided dose dependent protection against deleterious [negative] effects of stress on learning and memory … B-glucan possesses therapeutic potential against stress induced memory impairment, and this effect can be attributed to its normalizing effect on corticosterone levels.”

Leishmania braziliensis Infection – Beta Glucan: Dos Santos JC, Barroso de Figueiredo AM, et al, “B-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32″, Cell Rep, 28(10):2659-2672, PMID: 31484076, Sep 3 2019. Quote: “American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection …via a process called trained immunity, conferring non-specific protection from secondary infections. …monocytes trained with the fungal cell wall component B-glucan confer enhanced protection against infections caused by Leishmania brazillensis through the enhanced production of proinflammatory cytokines.”

Leprosy: Rayyan W, Delville J, “Effect of beta 1,3 glucan and other immunomodulators of microbial origin on experimental leprosy in mice.” Acta Leprol. 1:93-100. 1983.

Leptospirosis: Wang J, Jin Z, et al, “The preventable efficacy of B-glucan against leptospirosis,” PloS Negl Trop Dis, 13(11):e000789, PubMed:31675378 Nov 1, 2019. Quote: “B-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that B-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1B and IL-6) in vitro, indicating that B-glucan induces an enhanced inflammatory response against Leptospira [bacterial] infection.” Note: Leptospirosis is an infection caused by corkscrew-shaped bacteria. Signs and symptoms can range from none to mild such as headaches, muscle pains, and fevers to severe with bleeding from the lungs or meningitis.If the infection causes the person to turn yellow, have kidney failure and bleeding, it is then known as Weil’s disease.

Leukemia

Leukemia -Myelogenous: Vetvicka V, Vannucci L, Sima P, Richter J, “Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials,” Molecules, 24(7), 1251; doi 10.3390/molecules24071251, PMID: 30935016, Mar 30, 2019. Quote: “Another clinical trial studied the mushroom-derived glucan, Maitake, in myelodysplastic syndromes, which can progress to acute myelogenous leukemia. The results showed elevated functions of neutrophils and monocytes, particularly production of reactive oxygen species.” [Note: While mushroom sourced glucan is not the yeast cell sourced beta glucan isolate in almost all reported research in this data base, the potential benefit derived for this mushroom glucan was deemed sufficiently of interest for inclusion.}

Leukemia / Fungal Infection: Octabsi Z, Mattiuzzi G, Estey E, Kantarijars H, et al, “Beta-D-glucan as a diagnostic, adjunct for invasive fungal infections” validating Grauganum H, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome,” Clin INfect Dis. 39(3):199-205. 2004

Leukemia: DiLuzio NR, Williams DL, “Protective effect of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice,” Infect Immun 20(3):804-810. Dept of Physiology, Tulane U, New Orleans, LA.* Jun 1978. Quote: “These data denote that glucan enhances nonspecific resistance to S. aureus sepsis, promotes survival during leukemic episodes, and increases survival time of leukemic mice with experimentally induced staphylococcal infection.”

Leukemia: Stewart C.C., et al., “Preliminary Observations on the Effect of Glucan in Combination with Radiation and Chemotherapy in Four Murine Tumors,” Cancer Treat. Prep.; 62: 1867-72. 1978. Quote: “The efficacy of glucan in combination with BCNU chemotherapy was measured using the disseminated AKR transplantable leukemia; the combination yielded a high level of cures compared to no survival for either agent alone.”

Leukemia: Williams D.L, DiLuzio NR, “Glucan induced modification of experimental Staphylococcus aureus infection in normal, leukemic and immunosuppressed mice.” Adv Exp Med Biol 121(A):291-306. 1979.* Quote: “…A post-treatment regimen of glucan significantly enhanced survival of AKR/J mice with lymphocytic leukemia as well as leukemic mice with experimentally induced systemic staphylococcal infection.”

Leucopenia: Vetvicka V, Volny T, et al: “Glucan and resveratrol complex — possible synergistic effects on immune system.” U of Louisville, Dept of Pathology, Biomed Pad Mde Fac, Czech Republic 15(1)41-6; Jun 2007. Quote: “…both glucan and resveratrol complex stimulated phagocytosis of blood leukocytes, caused increase in surface expression of CD(+) splenocytes and showed higher restoration of spleen recovery after experimentally induced leucopenia [low white cell count]. In all these cases, strong synergetic effects were observed.“

Lewis lung carcinoma: Kogan G, Pajtinka M, Babincova M, Miadokova E, Rauko P, Slamenova D, Korolenko TA; “Yeast cell wall polysaccharides as antioxidants and antimutagens: can they fight cancer?” Inst of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia; Neoplasma 55(5):387-93 2008. Quote: “…yeast cell wall beta-D glucans reveal immunomodulating properties which allows for their application in anti-infective and antitumor therapy. The derivatives of beta-D-glucan exerted potent enhancement of tumor necrosis [killing] factor alpha (TNF-alpha) …and revealed synergistic effect with cyclophosphamide in the treatment of Lewis lung carcinoma and two types of lymphosarcoma in murine models. The results indicate protective antioxidant, antimutagenic and antigenotoxic [deters physical dna damage] activities…and imply their potential application in anticancer prevention/therapy.”

Lifespan: Song L, Zhour Y, et al, “Dietary intake of B-glucans can prolong lifespan and exert an anti-oxidant action of aged fish Nothobranchius guentheri,” Rejuvenation Res, PMID: 315191931, Oct 8 2019. Quote: “These data together suggest for the first time that B-1,3-glucans can extend the lifespan, delay the onset of age-related biomarkers and exert an antioxidant action of the aged fish N. guentheri. It also implies that B-1,3-glucans may be potentially useful for health care in the elderly, including extension of the lifespan.”

Lipid Metabolism Disorder: Pola P, “Composition for the prevention and/or treatment of lipid metabolism disorders and allergic forms,” U.S. Patent Application 20030017999, January 23, 2003. Quote: “beta-1,3-D-glucan has proved effective not only in preventing lipid metabolism disorders, but also in stimulating immune defenses, in preventing onset of tumors and in controlling serum glucose.”

Listeria – Bacterial Infection – Beta Glucan: Therooude C, Reverte M, et al, “Trained Immu7nity Confers Prolonged Protection from Listeriosis,” Front Immunol, 12:23393, https://doi.org/10.3389/fimmu.2021.723393, Sep 17 2021. Quote: “Trained Immunity refers to the ability of the innate immune system exposed to a first challenge to provide an enhanced response to a secondary homologous or heterologous challenge. We reported that training induced with B-glucan one week before infection confers protection against a broad-spectrum of lethal bacterial infections. …Altogether, these data suggest that training increases the generation and the antimicrobial activity of PMNs [polymorhonuclear neutrophils) and monocytes, which may confer prolonged protection from lethal bacterial infections.” Note: Listeriosis is a serious bacterial infection caused by the germ Listeria monocytogenes, usually caused by contaminated food.

Listeria: Torello CO, et al, “Immunohematopoietic modulation by oral B-1,3-glucan in mice infected with Listeria monocytogenes,” Int Immunopharmacology, Vo 10, Issue 12, P 1573-1579, Dec 2010. Quote: “In this study we demonstrated that the oral administration of B-1,3-glucan protects mice from a lethal dose of Listeria monocytogenes (LM) when administered prophylactically for 10 days at the doses of 150 and 300 mg/kg, with survival rates up to 40%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with LM, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow.” Note: Listeriosis is a serious bacterium infection usually caused by eating food contaminated with the bacterium Listeria monocytogenes – serious food poisoning.

Liver – hepatoprotective

Liver – Dectin-1 -Non-alcoholic fatty liver disease (NAFLD): Wang Min-xlu, Luo Wu, Ye Lin et al, “Dectin-1 plays a deleterious [harmful to health threat] role in high fat diet-induced NAFLD [non-alcoholic fatty liver disease] of mice through enhancing macrophage activation,” Acta Pharmacologica Sinica 120-132, June 10, 2022. Quote: “Dectin-1 was required for hepatic macrophage activation and inflammatory factor induction. …Condition media generated from Dectin-1 deficient macrophages failed to cause hepatocyte lipid accumulation and hepatic stellate activation. …[No Dectin-1, no activation] Dectin-1 in NAFLD through enhancing macrophage pro-inflammatory responses and suggest that it can be targeted to prevent inflammatory NAFLD.” [Note: Insoluble beta 1,3/1,6 glucan necessary activator of Dectin-1 receptor]

Liver – Environmental Toxins: Tuckman NB, Ozek DA, et al, “Beta-glucan effects on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in liver and brain,” Biotech Histochem, 1-8, PMID: 35073792, https://doi.org/10.1080/10520295.2022.2025902 , Jan 25, 2022. Quote: “2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental contaminant that is toxic to brain, heart, kidney and liver. TCDD toxicity is due to free radical formation. …The oxidative stress and histopathology caused by TCDD were ameliorated by beta-glucan treatment. Beta-glucan should be explored for preventing brain and liver damage caused by TCDD toxicity.”

Liver / hepatic glucose: Cao Y, Zou S, et al., “Orally Administered Baker’s Yeast B-Glucan Promotes Glucose and Lipid Homeostasis in the Livers of Obesity and Diabetes Model Mice,” J Agric Food Chem, 8;65(44):9665-9674, PMID: 29035040; Nov 2017. Quote: “BYG [Baker’s yeast glucan] “It was found that [orally administered] BYG decreased the blood glucose and the hepatic glucose and lipid disorders. …All these findings demonstrated that Baker’s Yeast Glucan (BYG) is beneficial for regulating glucose and lipid homeostasis in diabetic mice, and thus has potential applications in anti-diabetic foods or drugs.”

Liver – hepatoprotective: Cao Y, et al, “Hypoglycemic activity of the Baker’s yeast B-glucan in obese/type 2 diabetic mice and the underlying mechanism,” Mol Nutr Food Res, 60(12):2676-2690, doi: 10.1002/mnfr.201600032, PMID: 27396408, Dec 2016. Quote, “…Meanwhile, BYGlc [pure B-glucan] promoted glycogen synthesis and inhibited fat accumulation in liver… .”

Liver – hepatoprotective: Steir H, Ebbeskotte V, Gruenwald J, “Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan,” Nutr J; 13;38, PMID 24774968, Apr 28, 2014. Quote: “…several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect. ,,,Further, numerous studies reported other health benefits of B-glucans, including hepatoprotective [prevents liver damage], wound healing, weight loss, antidiabetic and cholesterol lowering functions.”

Liver Damage: Sugiyama A, Suzuki K, et al, “Hepatoprotective effects of paramylon, a beta-1-3-D-glucan isolated from Euglena gracilis Z, on acute liver injury induced by carbon tetrachloride in rats.” Vet Med Sci Japanese Soc Vet Sci 71(7):885-890, PMID: 19652474, July 2009. Quote: “The treatment of paramylon [beta-(1-3)-D-glucan] recovered reductions of activity of hepatic superoxide dismutase, catalase and glutathione peroxidase induced by CCI(4) [carbon tetrachloride]. These results demonstrate that paramylon [beta-(1-3)-D-glucan] exhibits protective action on acute hepatic injury induced by CCI(4) [carbon tetrachloride] via an antioxidative mechanism.”

Liver Damage: Sener G, Eksioglu-Demiraop E, Cetiner M, Ercan F, Yegen BC; “beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects.” European J Pharmacology; 542(1-3):170-178; Epub May 2006. Aug 7 2006. Quote: “Methotrexate is an antifolate [antimetabolite chemotherapy drug] that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae [disease condition caused by a disease], where oxidative stress [free radical damage] is noticeable. … Thus, the findings of the present study suggest that beta-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis [white immune cell death], oxidative [free radical] tissue injury and thereby the intestinal and hepatorenal [liver or kidney] side effects of methotrexate treatment.”

Liver Toxicity/Oxidative Free Radical Injury: Toklu HZ, Sehirili AO, Velioglu-Ogunc A, Centinel S, Sener G; “Acetaminophen-induced toxicity is prevented by beta-d-glucan treatment in mice.” European J Pharmacology; 543(1-3):133-40; Epub 2006 Jun; Jun 2, 2006. Quote: “The protective effect of beta-glucan against oxidative injury caused by acetaminophen [Tylenol, Anacin 3, Tempra, Datril] was studied in mice liver…Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content. Similarly, serum ALT, AST levels, as well as LDH and TNF-alpha, were elevated in the acetaminophen-treated group…beta-d-glucan treatment reversed all of these [liver toxicity] biochemical indices, as well as histopathological alterations that were induced by acetaminophen. In conclusion, these results suggest that beta-d-glucan exerts cytoprotective effects against oxidative injury through its antioxidant properties and may be of therapeutic use in preventing acetaminophen toxicity.”

Lung Cancer: Roudi R, Mohammadi SR, Roubary M, Mohsenzadegan M, “Lung Cancer and B-glucans: review of potential therapeutic applications,” Invest New Drugs 10.1007/s 10637-017-0449-9, , Mar 16, 2017. Quote: “β-glucans…potentiate the immune system against microbes and toxic substances. Moreover, β-glucans are known to exhibit direct anticancer effects and can suppress cancer proliferation through immunomodulatory pathways. …Numerous researchers are now dedicated to using B-glucans as a therapy for lung cancer.”

Lung Injury – Sepsis: Abdulkadir B, Mustafa K, et al, “Beta-Glucan Attenuates Inflammatory Cytokine Release and Prevents Acute Lung Injury in an Experimental Model of Septis,” Shock, Vol 27(4) p397-401, DOI: 10.1097/01.shk.0000245030.24235.f1, Apr 2007. Quote: “In this study we investigated the putative protective role of B-glucan against sepsis-induced lung injury. …The present study demonstrates that B-glucan, a clinically relevant nonspecific immunomodulator, can significantly attenuate the expression of proinflammatory cytokines and systemic inflammation in rat after sepsis. We have also shown that B-glucan can affect the lethality and occurrence of acute lung injury as measured through end-organ histological damage in response to sepsis. …

Lung Damage – Sepsis: Babayigit H, Kucuk C, et al, “Protective effect of beta-glucan on lung injury after cecal ligation and puncture in rats.” Department of General Surgery, School of Medicine, Erciyes University, 38039, Kayseri, Turkey; Intensive Care Med. (6):865-70; Jun 31, 2005. Quote: “In this rat model of intra-abdominal sepsis beta-glucan treatment partially protected against secondary lung injury, decreased lung hemorrhages, and lung neutrophilia. These results suggest that beta-glucan protects against sepsis-associated lung damage.”

Lupus – See Auto-Immune Disorders

Lymphopenia & Neutropenia: Sima P, et al, “Effects of glucan on bone marrow.” Ann Transl Med. ; 2(2)18. PMC 4202472; Feb 2014. Quote: “The extensive research studying various effects of glucans on bone marrow showed significant restoration of both lymphopenia and neutropenia. … glucan might be widely used as radioprotectant that could mitigate the biological effects of radiation exposure both in cases of radiation accidents or in medically used irradiation.”

Lympho-sarcoma Cancer: Kogan G, Pajtinka M, Babincova M, Miadokova E, Rauko P, Slamenova D, Korolenko TA; “Yeast cell wall polysaccharides as antioxidants and antimutagens: can they fight cancer?” Inst of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia; Neoplasma 55(5):387-93 2008. Quote: “…yeast cell wall beta-D glucans reveal immunomodulating properties which allows for their application in anti-infective and antitumor therapy. The derivatives of beta-D-glucan exerted potent enhancement of tumor necrosis [killing] factor alpha (TNF-alpha) …and revealed synergistic effect with cyclophosphamide in the treatment of Lewis lung carcinoma and two types of lymphosarcoma in murine models. The results indicate protective antioxidant, antimutagenic and antigenotoxic [deters physical dna damage] activities…and imply their potential application in anticancer prevention/therapy.”

M

Macrophages

Macrophages: Fatima N, Upadhyay T, et al, “Particulate Beta-Glucan Induces Early and Late Phagosomal Maturation in Murine Macrophages,” Front Biosci, 9, 129-140, PMID: 27814595, Jan 1, 2017. Quote: “Beta-glucans bind to glucan receptor[s] on phagocytic cells and modify these cells to become ‘immunologically active’ by generating a variety of innate immune responses. Here, we report that yeast-derived beta-glucan particles of a specific size are easily phagocytosed by macrophages and induce the production of ROS [antimicrobial reactive oxygen species].”

Macrophages: Athens JW et al, “Chapter 12. The Reticuloendothelial (Mononuclear Phagocyte) System and the Spleen,” Wintrobe’s Clinical Hematology, Ninth Editon, Lea & Febiger, Philadelphia PA, pp. 311-325 1993. Quote: “RES phagocytes are found in large quantities in the spleen (sinusoidal cells), lymph nodes (lymphocytes), and lungs (alveolar macrophages). But the Kupffer cells in the liver represent about 50% of all macrophages in the human body. Other macrophages are present in smaller numbers in the blood (monocytes), brain (microglia), kidney (mesangial cells), bone marrow, adrenals, thymus, mucous membranes, serous cavities, breast, placenta and connective tissue (histiocytes). The human RES (immune system] consist of at least 200 billion phagocytic cells.” Note: Approximately 20 trillion cells in the immune system total.

Macrophages/THP-1 cell line: Auwerx J, “The human leukemia cell line, THP-1: a multifaceted model for the study of monocyte-macrophage differentiation,” Experientia, 47(1):22-31, PMID: 1999239, DOI: 10.1007/BF02041244, Jan 15 1991. Quote: “THP-1 is a human monocytic leukemia cell line. …THP_1 cells differentiate into macrophage-like cells which mimic native monocyte-derived macrophages in several respects. Because of these characteristics, the THP-1 cell line provides a valuable model for studying the mechanisms involved in macrophage differentiation, and for exploring the regulation of macrophage-specific genes as they relate to physiological functions displayed by these cells.” Note: THP-1 cells are frequently used in research studies as almost equivalent cells to act as a multifaceted model for human macrophages.

Marathon Athletes – See also “Respiratory”

Marathon Runners-Human Trial -Upper Respiratory Tract Infection: Mah E, Kaden VN, Kelley KM, Liska DP, “Soluble and Insoluble Yeast B-Glucan Differentially Affect Upper Respiratory Tract Infection in Marathon Runners: A Double-Blind, Randomized Placebo-Controlled Trial,” J Med Food, doi:10.1089/jmf.2019.0076, PMID: 31573387, Oct 1 2019. Quote: “…Total severity of URTI [Upper Respiratory Tract Infection] was significantly lower in the insoluble yeast B-glucan group compared to the placebo group. …Severity ratings for nasal discharge was significantly lower in both the insoluble and soluble yeast B-glucan groups compared to the placebo groups. …severity rating for sore throat was lower in the insoluble, but not the soluble yeast B-glucan group compared to the placebo group. …The insoluble yeast B-glucan group, but not the soluble yeast B-glucan group also reported fewer URTI symptomatic days compared to the placebo group.”

Marathon Runners – Exercise – Strenuous: McFarlin BK, Venable AS, “Oral Supplementation with Baker’s Yeast Beta Glucan is Associated with Altered Monocytes, T Cells and Cytokines following a Bout of Strenuous Exercise;” Front Physiol, 8:786, PMID 29104540, PMCID: PMC5654840, Oct 20, 2017. Quote: “Exercise and physical labor in extreme environmental conditions causes transient decreases in immune cell and cytokine concentrations, likely increasing the susceptibility to opportunistic infection. …oral BYBG [Baker’s Yeast Beta Glucan] supplementation modulates the expected exercise response for individuals of average fitness. This may result in a decrease in susceptibility to opportunistic infections after strenuous exercise.”

Marathon Runners – Exercise – Strenuous-Human Study: Carpenter KC, Breslin WL, McFarlin BK, et al, “Baker’s yeast B-glucan supplementation increases monocytes and cytokines post-exercise: implication for infection risk?”, ABr J Nutr, 109(3):478-86, PMID: 22575076, Feb 14 2013. Quote: “Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with …bakcr’s yeast B-glucan could minimize post-exercise immunosuppression. …It appears that 10 d[ays] of supplementation with BG [baker’s yeast B-glucan] increased the potential of blood leukocytes for the production of IL-2, IL-4,IL-5 and IFN-y. The key findings of the present study demonstrate that BG [baker’s yeast B-glucan] may have potential to alter immunity following a strenuous exercise session.”

Marathon Runners – Respiratory: Talbott SM, Talbot JA, “Effect of Beta 1,3/1,6 Glucan on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes,” J Sports Sci Med, 8(4):509-515, PMID 24149590, Dec 1, 2009. Quote, “Beta-Glucan supplementation reduces post-exercise upper-respiratory tract symptoms (URTI) in marathon runners. Maintenance of post-exercise immune function is associated with improved mood state, including reduced fatigue and increased vigor in athletes.”

Marathon Athletes – Physical or Emotional: Carrow, D.J.; “Beta-1,3-glucan as a Primary Immune Activator,” Townsend Letter; June 1996. Quote: “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”

Melanoma – Cancer : Eom Su Jin, Lim ae-Gyu, et al, “Inhibitory effect of Saccharomyces cerevisiae extract obtained through ultrasound-assisted extraction on melanoma cells,” 76:105620, PMID: 34119906, https://doi.org/10.1016/j.ultsonch.2021.105620 . Aug 2021. Quote: “…the extract reduced melanoma tumor volume… resulting in an increased total extraction and B-glucan yields of 73.6% and 7.1%, respectively, compared with that achieved using a conventional chemical (0.5M NaOH) extraction method. Taken together, the results of this study suggest that UAEY [ultrasound-assisted extract of yeast containing beta glucan] may represent an effective anti-skin cancer agent.”

Melanoma – Cancer : Vetvicka V, Vetvickova J, “Glucan Supplementation Has Strong Anti-melanoma Effects: Role of NK Cells”, Anticancer Res. 35(10):5287-92. PMID: 26408688. Oct 2015. Quote: “…we focused on possible effects of insoluble yeast-derived β-glucan on the growth of melanoma cells.… glucan supplementation had a strong-positive effect in both reducing tumor weight, lung colonies and overall survival rate of tested animals. In addition, glucan inhibited the damage to blood cells and potential effects of regular chemotherapy.”

Memory, Cognition, Beta Glucan & the Gut-Brain Axis: Hu Minnin, Zhang P, Wang R, et al, “Three Different Types of B-Glucans Enhance Cognition: The Role of the Gut-Brain Axis,” Front Nutr, 9:848930, eCollection 2022, PMID: 35308288, https://doi.org/10.3389/fnut.2022.848930 , Mar 3, 2022. Quote: “Dietary fiber is fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of cognition and brain function via the gut-brain axis. This study aimed to compare the effects of B-glucans …representing B-(1,3)/(1,6)-glucan, B-(1,3) glucan or B-(1,3)/(1,4)-glucan on cognition and the gut brain axis. All three supplementations with B-glucans enhanced the temporal order recognition memory. …[B-(1,3)/(1,6)-glucan] significantly increased the post-synaptic thickness of synaptic ultrastructure in the PFC whilst the other two B-glucans [B-(1,3) and B-(1,3)/(1,4)] had no significant effect. In the colon, every B-glucan supplementation increased the number of CD206 positive cells and promoted the expression of IL-10 and reduced IL-6 and TNF-alpha expression.”

Memory Impairment-Stress Induced Cognitive Decline: Khan SH, Khan S, et al, “B-1,3-Glucan attenuated chronic unpredictable mild stress induced cognitive impairment in rodents via normalizing corticosterone levels,” Cent Nerv Syst Agents Med Chem, PMID: 32778039, https://doi.org/10.2174/1871524920666200810142359, Aug 10 2020. Quote: “Chronic stress elevates the cortisol beyond normal levels which affects cognition including learning and memory. … Results of the current study revealed the B-glucan provided dose dependent protection against deleterious effects of stress on learning and memory … B-glucan possesses therapeutic potential against stress induced memory impairment, and this effect can be attributed to its normalizing effect on corticosterone levels.”

Meningitis – Cryptococcal – fungal: Hester MM, Lee CK, Abraham A, et al, “Protection of mice against experimental cryptococcosis [fungus] using glucan particle-based vaccines containing novel recombinant antigens,” Vaccine, SO264-410X(19)31431-8, PMID: 31699504, Nov 4 2019. Quote: “Meningitis due to Cryptococus neoformans is responsible for upwards of 180,000 deaths worldwide annually, mostly in immunocompromised individuals. Currently there are no licensed fungal vaccines, and even with anti-fungal drug treatment, cryptococcal meningitis is often fatal. …Our lab previously demonstrated vaccination with recombinant cryptococcal proteins delivered in glucan particles (GPs) protects mice against an otherwise lethal infection. …These screens highlight the efficacy of Glucan-particle-subunit vaccines and identify promising antigens for further testing in anti-cryptococcal, multi-epitope vaccine formulations.”

Meningococcal disease: Qiao W, Shaoyang J, et al, “Conjugation of B-glucan markedly increase the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine,” Vaccine, 33(17):2066-72. PMID: 25728319, DOI: 10.1016/j.vaccine.201.02.045, Apr 21, 2015. Quote: “Meningococcal disease is a fatal illness of sudden onset caused by Neisseria meningitides. … As a stimulator of humoral and cellular immunity, B-glucan can activate macrophages and trigger intracellular processes to secrete cytokines … . Presumably, conjugation of B-glucan ensured the two components to simultaneously reach the antigen presenting cells [APC] and stimulate the immune response. …Thus, conjugation of B-glucan is an effective strategy to markedly improve the CPS-specific immunogenicity of the conjugate vaccine.

Mercury-thimerosal – Vetvicka V, “Effects of B-glucan on some environmental toxins: An overview.” Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub; 158(1):1-4. PMD: 24399292. 2014; Quote: “…glucan reduces the immunosuppressive effects of a number of agents including chemo therapy and radiation. … An overview of the effects of glucan on the mycotoxin, aflotoxin and other environmental toxins (mercury-thimerosal, depleted uranium). Glucan is effective as a natural immunomodulator and could be used as an inexpensive solution to reducing the adverse effects of some environmental toxins.”

Mercury – Vetvicka V, “Effects of glucan on immunosuppressive actions of mercury,” J Med Food, 12(5):1098-104, PMID 19857075, Oct 2009. Quote: “The well established negative effects of mercury on the immune system led us to the study… . Our results showed that glucans can be successfully used as a natural remedy of low-level exposure to mercury.”

Metabolic Dysfunctions: Cordero JG, Ruiz BS, et al, “Effectiveness of hydroxycinamates and beta-glucans as dietary tools against obesity and its associated dysfunctions, and their application as nutraceuticals,” Nutr Hosp, Vol 37, Num 5, pp 887-1092, PMID: 32960625, DOI: 10.20960/nh.031125, Sep 22 2020. Quote: Obesity has been related to disorders such as type-2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, among others, which has made of obesity the second cause of preventable death, only behind smoking. Among bioactive compounds, this study will focus on B-glucans, … and hydroxycinnamic acids, …compounds show complex and multifactorial effects, acting as hypolipemic, hypoglycemic, antioxidant, prebiotic and satiating agents. They act by modulating different metabolic pathways, affecting the absorption and metabolism of lipids and carbohydrates, reducing oxidative damage, promoting the proliferation of beneficial bacterial species, and reducing dietary intake.. It may be concluded that …beta-glucans …have potential as a nutritional tool for management of obesity and associated metabolic dysfunctions.” Note: Research in Spanish

Metabolic Stress – Obesity: Muthuramalingam K, Singh V, et al, “Dietary intervention using (1,3)/(1,6)-B-glucan, a fungus-derived soluble prebiotic ameliorates high-fat diet-induced metabolic distress and alters beneficially the gut microbiota in mice model,” Eur J Nutr, doi: 10.1007/s0394-019-021, Pubmed: 31664519, Oct 29 2019. Quote: “B-glucan consumption exhibited anti-obesity property in mice groups fed with HFD [High Fat Diet]. In addition, B-glucan ameliorated HFD-induced hepatic stress, colonic motility and intestinal atrophy (reduction in colon length, goblet cells, and mucosal layer thickness). Further, B-glucan incorporation shifted bacterial community by increasing butyrate-producing bacteria such as Anaerostipes, Coprobacillus, and Rosebery and decreasing reportedly obesity-associated bacteria such as Parabacteroides and Lactococcus.”

Metabolic Syndrone – See Diabetes

Metastasis – Cancer – “The effects of B-glucans on cancer metastasis,” Anticancer Agents Med Chem, 13(5) 699-708, PMID: 23140352, Jun 2013. Quote: “An immunomodulating agent, B-glucan acts through the activation of innate immune cells such as macrophages, dendritic cells, granulocytes and natural killer cells. This activation triggers the responses of adaptive immune cells such as CD4 or CD8 T cells and B cells, resulting in the inhibition of tumor growth and metastasis.”

Methotrexate (MTX): Koc F, Erisgin Z, Tekehoglu Y, Takir S, “The effect of beta glucan on Methotrexate (MTX) induced testicular damage in rats.” Biotech Histochem, 1-6, PMID 29363342, Jan 24, 2018. Quote: “Histopathology was reduced in the methotrexate (MTX) + beta glucan (BG) group compared to the MTX group. …We found that methotrexate (MTX) causes deleterious[harmful] effects on testicular tissue and that beta glucan may be protective.” Note: “histopathology” – changes in tissues caused by disease.

Methotrexate Toxicity: Sener G, Eksioglu-Demiraop E, Cetiner M, Ercan F, Yegen BC; “Beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects.” European J Pharmacology; 542(1-3):170-178; Epub May 2006. Aug 7 2006. Quote: “Methotrexate is an antifolate that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae [disease condition caused by a disease], where oxidative stress is noticeable. … Thus, the findings of the present study suggest that beta-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis [white immune cell death], oxidative tissue injury and thereby the intestinal and hepatorenal [liver or kidney] side effects of methotrexate treatment.”

Microbes: Lablanc BW, Albina JE, Reichner JS, “The effect of PGG-{beta}-glucan on neutrophil chemotaxis in vivo.” Dept of Surgery, Rhode Isl Hospital and Brown Med Sch. Providence. J Leukoc Biol Jan 13, 2006. Quote: “The beta-glucans are long-chain polymers of glucose in beta-(1,3)(1,6) linkages, which comprise the fungal cell wall and stimulate cells of the innate immune system. …Taken together, these findings demonstrate that beta-glucan directly affects the chemotactic capacity of circulating neutrophils…and potentiates antimicrobial host defense.”

Microbes: Brown GD, Gordon S; “Immune recognition. A new receptor for beta-glucans.” Sir William Dunn School of Pathology, University of Oxford, Nature 6;413(6851):36-7. Sep 2001. Quote: “The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system – stimulating antitumor and antimicrobial activity, for example – by binding to receptors on macrophages and other white blood cells and activating them.”

Microbial Infection: Camilli G, Tabouret G, Quintin J, “The Complexity of Fungal B-Glucan in Health and Disease: Effects on the mononuclear Phagocyte System,” Front Immunol, 16:9:673, PMID 29755450, Apr 16, 2018. Quote: “Study of this molecule [B-glucan] has been motivated by its importance as a pathogen-associated molecular pattern upon fungal infection as well as by its promising clinical utility as biological response modifier for the treatment of cancer and infectious diseases. Its immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils and natural killer cells. …B-glucans exhibit antitumor and antimicrobial activities by modulating the biologic responses of mononuclear phagocytes [macrophages et al].” Note: A Pathogen-associated molecular pattern (PAMP) is a distinct evolutionarily conserved structure on pathogens detected by pattern recognition receptors (PRRs), with PRRS relied upon by the innate immune system in the defense against invading microbial pathogens.

Microbial Infection: Chen J, Seviour R; “Medicinal importance of fungal beta-(1–>3, (1–>6)-glucans.” Mycol Res, PMID 17590323, Jun;111(Pt6):635-52, 2007. Quote: “…beta-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes.”

Micronization: Particle Size, Microparticulate, Micronized (Also 1,000 nanos=1 micron)

NOTE: Conflicting Opinions: Micronization-Beta Glucan Particle Size: Vaclav Vetvicka PhD participated as an accredited Reviewer of an April 22, 2020 published article detailed below (Ham AB, et al, https://doi.org/10.3389/fimmu.2020.00658) that stated, “The particle size of glucan matters and its generally known that nanoparticles with a diameter 1–2 μm [microns] are better absorbed [enhanced bioavailability] by macrophages than large-size particles. Micronized is generally considered to be 1-5 microns in size. 1,000 nanometers = 1 micron or micrometer.

Previously, Vaclay Vetvicka authored, “Beta Glucan, Natures Secret-3rd Edition,” p 153-154, 2015. In his 2015 book is a Vetvicka’ quote in which Vetvicka stated: “It is apparent that, in the case of macrophages and phagocytosis, size really does not matter.” Note: Vaclay Vetvicka is the only beta glucan researcher, found to date (2022) , to assert particulate beta glucan particle size does not matter in conjunction with macrophages and phagocytosis. Further, Vetvicka’s website says he works in “cooperation” with A J Lanigan, who is the owner of multiple level beta glucan brands constantly claiming micronization of beta glucan is not based on authentic scientific and medical school research and is the pseudo science of a competing beta glucan manufacturer. The reader can read the extensive micronization research below and decide which and who is correct. Note: 1,000 nanos equals 1 micron.

Micronization-Nanoparticle – Carrier Composite (Doxorubicin): Huang J, Wu C, et al, “Chiral Active B-Glucan Nanoparticles for Synergistic Delivery of Doxorubicin and Immune Potentiation,” Int J Nanomedicine, 15-5083-5095, PMID: 32764938, https://doi.org/10.2147/UN.525814-5, Jul 14 2020. Quote: “B-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified. ….B-glucan nanoparticles can activate macrophages to produce immune enhancing cytokines (IL-1B, IL-6, TNF-alpha, IFN-y). This work demonstrates that B-glucans nanoparticles with special chiral feature which leading to strong immunopotentiation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer treatment.”

Micronization-Particle Size-Beta Glucan: Han AB, Baruah K, Cox E, et al-Reviewed by Vaclav Vetvicka, “Structure-Functional Activity Relationship of B-Glucans from the Perspective of Immunomodulation: A Mini-Review,” Front. Immunol., https://doi.org/10.3389/fimmu.2020.00658, April 22 2020. Quote: “Particle Size: The particle size of glucan matters and its generally known that nanoparticles with a diameter 1-2 μm [microns] are better absorbed by macrophages than large-size particles.”

Microparticulate Beta Glucan: Biao H, Baruah K, Cox E, et al, “Structure-Functional Activity Relationship of B-Glucans from the Perspective of Immunomodulation: A Mini-Review,” Front. Immunol., https://doi.org/10.3389/fimmu.2020.00658, Noted in the article as reviewed by Vaclav Vetvicka, U Louisville, U.S., Apr 22, 2020. Quote: “Particulate B-glucans isolated from yeast are hollow, porous 2-4 micron spheres with an outer shell capable of mediating uptake by phagocytic cells. …The particle size of glucan matters and its generally known that nanoparticles with a diameter 1-2 microns are better absorbed by macrophages than large-size particles.” [Note: 1,000 nanos equals 1.0 micron or 1.0 nano equals .001 microns.].

Micronization: Particle Size: Durrell K, Vetvicka V, “Beta-glucan: A space that ‘lacks the prestige’ of traditional nutrients, but holds great potential,” Nutrition Insight, pp1-2, www.nutritioninsight.com , Sep 04 2019. Quote: “Vetvicka further notes … due to their larger size, beta-glucans are normally not phagocytized by gut cells and, therefore, are blocked from entering the body. Note: Micronization significantly reduces beta glucan particle size to better enable enhanced phagocytosis and bioavailability.

Microparticulate Vaccine Delivery System: Vetvicka V, Vannucci L, ” B-glucan as a new tool in vaccine development,” Scand J Immunol, doi:10.1111/sji.12833, PMID 31544248, Sep 22 2019. Quote: “Among the numerous categories of particulate antigen [vaccine] delivery systems, …the Saccharomyces cerevisiae-derived B-glucan microparticles could be regarded as the most promising for an oral delivery platform. Particulate nanocarriers, which may exert a high adjuvant potential and could increase the immune response to vaccination due to their size and structural similarity to natural pathogens.”

Micronization: Gean PS, et al, “Micronization of trans-resveratrol by supercritical fluid: Dissolution, solubility and in vitro antioxidant activity, “Micronization,” doi.org/10.1016/j.indcrop.2017.11.008, Feb 1, 2018. Quote: “The micronization process is characterized by the reduction of particle size towards obtaining changes in physical structure and increase the dissolution rate, which leads to increased solubility of the compound and consequently greater bioavailability.”

Micronization – Nanoparticle Size: Zhang M, Kim Julian, et al, “Optimizing Tumor Microenvironment for Cancer Immunotherapy: B-Glucan-Based Nanoparticles,” Front Immunol, 9:341, PMC 5834761, Feb 26 2018. Quote: “This article reviews the development of B-glucan and B-glucan-based nano-particles as immune modulators of tumor microenvironment (TME). …we discuss the mechanisms of conditioning tumor microenvironment (TME) using B-glucan and B-glucan-based nano-particles, and how this strategy enables future design of optimal combination cancer immunotherapies. …A particulate B-glucans derived from yeast mediates antitumor immune responses by inducing pro-inflammatory cytokine secretion and stimulating innate immune effector cell activation.”

Microparticulate Beta Glucan: Baert K, et al, “Duality of B-glucan microparticles: antigen carrier and immunostimulants,” Int J Nanomedicine. 11: 2463–2469, . PMCID:PMC 4898424. May 31, 2016. Quote: “β-glucan microparticles (GPs) are emerging microparticles known for their safety, immunogenicity, and high antigen encapsulation efficiency. These promising antigen carriers are derived from the cell wall of Saccharomyces cerevisiae (Baker’s yeast). The resulting GPs [B-glucan microparticles] were hollow and porous biomimetic 2–5 µm [micron] particles consisting of >85% β-1,3-D-glucan polymers (β-glucans), ~2% chitin, and <1% lipids and proteins, with the rest being mostly ash and moisture.”

Micronization -Nanoparticle Size: Farris E, Brown DM, Ramer-ETait, Pannnier AK, “Micro-and nanoparticulates for DNA vaccine delivery” Exp Biol Med (Maywood) pii:1535370216643771; PMID: 27048557; April 4, 2016. Quote:“In contrast, nanoparticle encapsulation leads to increased internalization, overall greater transfection efficiency, and the ability to increase uptake across mucosal surfaces. Moreover, selection of the appropriate biomaterial can lead to increased immune stimulation and activation through triggering innate immune response receptors and target DNA to professional antigen presenting cells. Finally, the selection of materials with the appropriate properties to achieve efficient delivery through administration routes conducive to high patient compliance and capable of generating systemic and local (i.e. mucosal) immunity can lead to more effective humoral and cellular protective immune responses.” Note: 1 Nano = .001 Microns

Micronization /Particle Size: Vetvicka V, “Beta Glucan, Natures Secret-3rd Edition,” p 153-154, 2015. Quote: “It is apparent that, in the case of macrophages and phagocytosis, size really does not matter.” Note: V Vetvicka is the only researcher found to date (2022) to assert beta glucan micronization and particle size does not matter in conjunction with macrophages and phagocytosis . See the Note with Comment at the beginning of this Segment for more information.

Microparticulate Beta Glucan Vaccine Adjuvant: Berner VK, duPre S, Redelman D, Hunter KW Jr, “Microparticulate B-glucan vaccine conjugates phagocytized by dendritic cells activate both naive CD4 and CD8 T cells in vitro,” Cellular Immunology, U of Nevada School of Medicine, Dept of Microbiology, PMID 26549577, DOI: 10.1016/j.cellimm.2015.10.007, Nov 2, 2015. Quote: “The interaction between B-glucan and its receptors serves as an activating signal that promotes anti-fungal immunity, but fungal B-glucan also has a long history of use as an adjuvant to promote immune responses to tumors and other microorganisms. …Microparticulate B-glucan (MG) was shown to exhibit adjuvant activity when conjugated to a test vaccine antigen. …Recent studies have confirmed that B-glucan particles can be used to deliver vaccine antigen for oral immunization.”

Micronization – Nanomedicine [1,000 Nanos or nanometers = 1 Micron] Malinoski FJ, “The nanomedicines alliance: an industry perspective on nanomedicines,” NanoMedicine 10(8): 1819-20, PMID 25038497, Nov 2014. Quote: “The field of nanomedicines has expanded significantly in recent years in the breadth of compounds under development ….”

Micronized: Pacheco P, White D, Sulchek T, “Effects of microparticle size and Fc density on macrophage phagocytosis.” PLos One;8(4):e60989. PMID:23630577; PMCID:PMC363260 . https://doi.org/10.1371/journal.pone.0060989 . April 22 2013. Quote: “The percentage of phagocytic macrophages was found to be strongly dependent on both the particle size and the particle Fc density. …Interaction with the smaller particles (micronized 0.5 µm and 1 µm) at a low Fc density resulted in a greater percentage of phagocytic macrophages than with high Fc density. …Therefore, larger microparticles (micronized 3 µm and 4.5 µm) may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles (0.5 µm to 2 µm) can deliver bio-active substances to a greater percentage of the macrophage population.” Note: Fc is an antibody molecule known as the crystallizable fragment. µm = microns. Larger Particle sizes in this study were 3 to 4.5 µm (microns) However, particles from 5 to 100+ µm (microns) are considered aggregated or agglomerated and sometimes referred to as globular due to increased size and reduced phagocytic activity.

Micronized Particulate: De Smet R, Demoor T, et al, “B-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination,” J. Control Release 172(3):67 1-8, PMID: 24041710, https://doi.org/10.1016/j.jconrel.2013.09.007 Dec 28 2013. Quote: “B-glucan particles (GP) are efficiently internalized by human intestinal epithelial cell lines (Caco-2 and HT-29 cells), without exerting negative effects on cell viability. …B-glucan particles (GP) are able to deliver ovalbumin (OVA) via an oral route allowing efficient antigen presentation alongside adaptive immune activation… .”

Micronized Particulate: Pacheco P, et al, “Effects of microparticle size and Fc density on macrophage phagocytosis.” PLos One;8(4):e60989. PMID:23630577; PMCID:PMC363260 , https://doi.org/10.137/journal.pone.0060989 . April 22, 2013. Quote: “The percentage of phagocytic macrophages was found to be strongly dependent on both the particle size and the particle Fc density. …Therefore, larger microparticles (3 µm and 4.5 µm or microns ) may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles (0.5 µm to 2 µm) can deliver bio-active substances to a greater percentage of the macrophage population….The internalization of particles by macrophages is highly dependent on microparticulate size and Fc density with an overall trend of the average number of internalized particles decreasing as microparticle size increases [0.5 to 4.5 microns] and Fc density decreases.”

Note: Micronized particles of 0.5 to 4 microns increased internalized particles vs larger particles in excess of 4 microns. Larger Particle sizes in this study were 3 to 4.5 µm (microns) However, particles from 5 to 100+ µm (microns) are considered aggregated or agglomerated and sometimes referred to as globular due to increased size and reduced phagocytic activity. Fc is an antibody molecule known as the crystallizable fragment. µm = microns.

Micronization / Particle Size / Endocytosis: Keiji H, Hiroshi T, “Endocytosis of Particle Formulations by Macrophages and Its Application to Clinical Treatment,” Chapter 16; 0706, 2012. Quote: “Particle size is likely the primary factor that governs endocytic uptake of particles. The optimum size of particles for efficient endocytic uptake varies according to the cell type. Macrophage cells are able to ingest large particles having a diameter between 1 micron and 10 microns to eliminate invaders from outside the body. The optimal sizes of the particles for the uptake by alveolar macrophages [primarily in the lungs] range between 3 microns and 6 microns, but those by peritoneal macrophages and peripheral blood mononuclear cells are reportedly from 0.3 microns to 1.1 microns.” Note: Endocytosis is the process of actively transporting molecules into the cell by engulfing such molecules with the cell membrane. The term micronized in reference to beta 1,3/1,6 glucan particles refers to insoluble particles 5 microns or less in size, with uniformity in micronized particles in size in a dose an important variable.

Microparticulate Beta Glucan: Zechner-Krpan V, Petravic-Tominac V, Galovic P, Galovic V, Filipovic-Grcic J, Srecec S, “Application of Different Drying Methods on B-Glucan Isolated from Spent Brewer’s Yeast Using Alkaline Procedure” University of Zagreb, Agriculturae Conspectus Scientificus, Vol 75, No 1 2010. Quote: “The macrophage phagocytosis is more enhanced by microparticulate B-glucan than by its aggregated form. Biological activity of B-glucan can be improved by reducing the size of its particles. …The particles having 1-2 µm [microns] in diameter are optimally phagocytized by macrophages.”

Microparticulate Beta Glucan: Zechner-Krpan Vesna , Petrav V, Gospodari I, Sajli L, Senka Akovi, Filipovi-Gr J,“Characterization of b-Glucans Isolated from Brewer’s Yeast and Dried by Different Methods,” University of Zagreb, Faculty of Food Technology and Biotechnology, Department of Biochemical Engineering, Laboratory of Biochemical Engineering,Food Technol. Biotechnol. 48 (2) 189–197, 2010. Quote: “It is known that immunological activity of b-glucan depends on particle dimensions and can be improved by reducing the size of the particles….”

Microparticulate Beta Glucan: Wang G, Liu X, Hu Y, Liu H, “Ultrasonic Modification of the B-Glucans from Saccharomyces cerevisiae and it’s Effection on the Immunoactivity in Mice,” Journal of Food Science and Biotechnology, 4:19, The Chinese Academy of Agricultural Science, Beijing, 2008. Note: Wang et al sonicated large sized macroparticle yeast B-glucan (SCG) by ultrasonications at a working frequency of 18 to 21 kHz at 400 W, with a processing time of 24 s per cycle and an interval of 6 s for a total of 20 cycles. The modified [micronized] SCG (C-SCG) showed a uniform distribution of single particles, and the particle size distribution bandwidth was narrowed. Quote: “Saccharomyces cerevisiae (SCG) average diameter [was] reduced from 56.49 microns to 2.33 microns. …Because the diameter change [micronization] of SCG brought some influences to it’s immune activity, the immunoactivity of N-SCG [no modification SCG] were tested. The results showed that the lymphocyte proliferation, the hemolytic level and the activity of NK cells of the [modified] C-SCG groups increased 42.35%, 28.89% and 78.10%, respectively, compared to that of N-SCG [no modification] groups.”

Micronized Particulate: Champion JA, Walker A, Mitragotri S, “Role of particle size in phagocytosis of polymeric microspheres.” Pharmaceutical research 25: 1815–1821 . PMIC 18373181, PMC 2793372, 2008. Quote: “Particles possessing diameters of 2-3 microm exhibited maximal phagocytosis and attachment….”

Microparticulate Beta Glucan: Berner VK, Sura ME, Hunter KW Jr., “Conjugation of protein antigen to microparticulate beta-glucan from Saccharomyces cerevisiae: a new adjuvant for intradermal and oral immunizations,” Appl Microbiol Biotechnol, 80(6):1053-61. PMID: 18677470, Oct 2008. Quote: “Our laboratory has prepared and characterized a novel microparticulate beta-glucan (MG) from the budding yeast Saccharomyces cerevisiae. …These results suggest that protein antigens can be conjugated to MG [microparticulate beta-glucan] via a carbodiimide linkage and that these conjugates provide an adjuvant effect for stimulating the antibody response to the protein antigens.”

Micronization: Zhongguo ZZ, “Research progress of microparticles as drug delivery system for traditional Chinese medicine [TCM]“, Maateria Medica, 32(5):371-374, [Chinese] PMID 17511135, Mar 01 2007. Quote: “Microparticle preparation, a new drug delivery system based on micro-encapsulation technique, includes micro-spheres and microcapsules. TCM microparticles can perform several sound characteristics and functions …such as controlled release, effect of targeting, increasing bioavailability or low toxicity. This makes it possible that TCM may exert much higher therapeutic efficacy and show lower side-effects as well.”

Micronization: Spence JK, et al, “Increased dissolution rate and bioavailability through co-micronization with microcrystalline cellulose,” Pharm Dev Technol, 10(4);451-60, PMID 16370174, 2005. Quote: “Micronization is a commonly used enabling technology to improve the bioavailability of compounds where absorption is dissolution rate limited.”

Micronization: Rasenack N, Muller BW, “Micron-size drug particles: common and novel micronization techniques,” Pharm Dev Technol; 9(1):1:14, ; PMID 1500462 2004; Quote: “Many drugs, especially newly developed substances, are poorly water soluble, which limits their oral bioavailability. The dissolution rate can be enhanced by using micronized drugs.”

Microparticulate Beta Glucan: Jordan F, Hunter Jr. KW, Gault R, “Method for preparing small particle size glucan in a dry material,” U.S. Patent 6,476,003. November 2002. Quote: “The greater generation and/or production of NO (Nitric Oxide) demonstrates the enhanced activity of the macrophage with a small particle size glucan which is indicative of an activity level of an immune system. … The measurement of NO production is indicative of an oxidative burst that kills and/or destroys the ingested microbes and/or particles by the macrophage. As a glucan re-aggregates into particles of greater than one micron in diameter, it appears to pass through an animal or human digestive system without substantially complete absorption……. As the glucan re-aggregates to a size of greater than one micron in diameter, some of the beneficial effect of the glucan is not achieved because the macrophage receptors are not activated as readily by glucan greater than one micron in diameter because the receptor size on corresponding cells and molecules that accept the glucan is generally about one micron in size. …The greater percentage phagocytosis demonstrates the enhanced activity of the macrophage and the small particle size glucan’s ability to activate the immune system.”

Microparticulate Beta Glucan: Hunter KW, Gault RA, Berner MD, “Preparation of microparticulate B-glucan from Saccharomyces cerevisiae for use in immune potentiation.” Letters in Applied Microbiology,” Vol 35 Issue 4, 267-271, PubMed 12358685, October 2002 (commercially MG Beta Glucan) Quote: “…there was evidence that macrophages, key target cells for the immunopharmacological activity of B-glucans, preferentially ingest particles in the 1-2-µ (micron) diameter size range. …Compared with the aggregated [5-100-µ micron diameter] form of B-glucan, the B-glucan microparticles remain in suspension longer for pharmaceutical applications… . Although both aggregated and microparticulate glucans enhanced peritoneal macrophage activation when administered orally in mice, the microparticulate glucan was significantly better than the aggregated form. …This microparticulate beta-glucan …following oral administration at 0.1 mg kg(-1) for 14 d, enhanced phagocytosis of mouse peritoneal macrophages significantly better than did aggregated beta-glucan particles.…A microparticulate form of beta-glucan that remains in suspension longer for pharmaceutical applications and has superior immune potentiation characteristics has been developed. [0.1 mg kg(-1)=7.5 mg per day for a 165 lb person]”

Microparticulate Beta Glucan: Donzis B. A.; Substantially purified beta (1,3) finely ground yeast cell wall glucan composition with dermatological and nutritional uses; U.S. Patent 5702719; 1997. Quote: “The preferred particle size of the find grind glucan product is about 1.0 micron or less and more preferably, .20 microns or less.” [=1000 to 200 nanometers orless; 1.0 micron = 1/25,400 of an inch]

Micronized Particulate: Tabata Y, Ikada Y, “Effect of the Size and Surface-Charge of Polymer Microspheres on Their Phagocytosis by Macrophage.” Biomaterials 9: 356–362. PMID 3214660 1988. Quote: “It was found that the maximal phagocytosis of polystyrene and phenylated polyacrolein microspherestook place when their size was in the range 1.0-2.0 microns.”

Microparticulate Beta Glucan: Artursson P, Edman P, Ericsson JL, “Macrophage stimulation with some structurally related polysaccharides.” Scand J Immunol;25(3):245-54. PMID:349430 Mar 1 1987 . Quote: “The macrophage-stimulating properties of some structurally related polysaccharides were studied in vitro. When the polysaccharides were presented to the macrophages as microparticles, they induced the release of interleukin 1 (IL-1) from the macrophages. ...Microparticulate 1.3-beta-glucan (curdlan) induced nonspecific macrophage mediated tumour cell killing while 1.4-alpha-glucan( starch), 1.6-alpha-glucan (dextran), and 1.6-alpha-mannan were without effect. The corresponding soluble polysaccharides did not stimulate the macrophages.”

Microparticulate Beta Glucan: Artusson P, Arro E, Edman P, Ericsson JL, Sjoholm l, “Biodegradable microspheres. V: Stimulation of macrophages with microparticles made of various polysaccharides,” J Pharm Sci ;76(2):127-33; PubMed 3572750 Feb 1987. Quote: “The interaction between four different microparticulate drug carriers and macrophages was investigated in vitro. The microparticles, consisting of …lichenan (1,3-beta-D-glucan) …were investigated for their macrophage stimulatory properties. …. Microparticles made of crosslinked lichenan [1,3-beta-D-glucan] were most stimulatory,….”

Microparasitic Diseases : DiLuzio N.R. and Williams D.L., “ The Roll of Glucan in the Prevention and Modification of Microparasitic Diseases;” Immunology Medicine, Alan R. Liss, Inc.; pp. 443-456. 1984. Quote: “Mindful of the extremely high rate of atherosclerotic complications and the extraordinary requirements for antioxidants in diabetic patients, the use of beta –1,3 glucan becomes an obvious adjunct for improved lifestyle under these conditions.“:

Microspheres: M.J. Auger, J.A. Ross, in: C.E. Lewis, J.O’D. McGee (Eds.), “Influence of microsphere size, composition, concentration and surface property,. The Natural Immune System: The Macrophage, Oxford University Press, New York, , pp. 2–74 1992. Quote: “The influence of … size of microspheres on their phagocytosis by mouse peritoneal macrophages were studied by using polystyrene and phenylated polyacrolein microspheres of different diameter… .. Size: maximum phagocytosis took place when their size was in the range of 1-2 μm [microns]….” Note: Microsphere is a term used for small spherical particles, with diameters in the micrometer/micron range (typically 1μm/micron to 1000μm (1mm)).

Microspheres: Tabata Y, Ikada Y, “Effect of the Size and Surface-Charge of Polymer Microspheres on Their Phagocytosis by Macrophage.” Biomaterials 9: 356–362. PMID 3214660 1988. Quote: “It was found that the maximal phagocytosis of polystyrene and phenylated polyacrolein microspherestook place when their size was in the range 1.0-2.0 microns.”

Middle Ear Infection-Acute Otitis Media: Cetinkaya EA, Ciftci O, et al, “What is the effectiveness of beta-glucan for treatment of acute otitis media?” Braz J Otorhinolaryngol, PMID: 32273203, DOI: 10.1016/j.bjori.2020.02.004, Mar 19 2020. [animal study] Quote: “Co-administration of antibiotic and beta-glucan led to a significant reduction in tympanic membrane thickness, inflammation, and epithelium damage…it can be suggested that beta-glucan, in combination with antibiotics may provide an alternative for the treatment of acute otitis media.”

Modulation: Tsujinaka T., Yokota M.K.; Modification of septic processes by B-glucan administration. Eur Surg Res; 22:540-546, 1990.*

Modulation: Rasmussen LT, Seljelid R, “The modulatory effect of lipoproteins on the release of interleukin 1 by human peritoneal macrophages stimulated with beta-1,3-D-polyglucose derivatives.” Apr 1989.*

Modulation: Patchen M.L., Lotzova E.; Modulation of murine hemopoiesis by glucan; Exp Hermatol 8: 409-422, 1980.

Modulation: Mansell P.W.A., Rowden G., Hammer C.; Clinical experiences with the use of glucan. Chirigos MA, ed.; Immune Modulation and Control of Neoplasia by Adjuvant Therapy. Raven Press, New York 255-280; 1978.

Mold – See Fungus

Monoclonal Antibodies and Beta Glucan:

Monoclonal Antibodies and Beta Glucan: Ziang [Xiang] D, Sharma VR, Freter CE, Yan J, “Anti-tumor Monoclonal Antibodies in Conjunction with B-Glucans: A Novel Anti-Cancer Immunotherapy,” Curr Med Chem, 19(25); 4298-305, PMID: 22834812, https://doi.org:10.2174/092986712802884303, 2013. Quote: “…particulate yeast-derived B-glucan stimulates both innate and adaptive anti-tumor immune responses. …B-glucan, has shown very promising and exciting results in pre-clinical animal models and early phase human clinical trials. The active components of yeast-derived B-glucan exert their unique immune stimulating functions by binding specifically to complement receptor 3 (CR3) via lectin-like domain (LLD) and activating CR3 to promote cellular cytotoxicity of iC3b-coated cancer cells.”

Monoclonal – Antibodies (mAbs) Cancer: Liu J, Gunn L, Hansen R, Yan J, “Combined yeast-derived beta-glucan with anti-tumor monoclonal antibody for cancer immunotherapy,” Exp Mol Pathol, 86(4):208-14; Jun 2009. Quote: “Beta-glucan is an immuno-stimulating agent that has been used to treat cancer and infectious disease for many years .. . Recent studies have unraveled the action mode of yeast-derived beta-glucan in combination with anti-tumor monoclonal antibodies (mAbs) in cancer therapy. ….Pre-clinical animal studies have demonstrated the efficacy of combined beta-glucan with anti-tumor mAb therapy in terms of tumor regression and long-term survival.”

Monoclonal Antibodies and Beta Glucan: Li B, Allendorg DJ, et al; “Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway,” J Immunol, Aug 1;177(3): 1651-9 PMID 16849475, 2006. Quote: “Anti-tumor mAbs hold promise for cancer therapy, but are relatively inefficient. Therefore, there is a need for agents that might amplify the effectiveness of these mAbs. One such agent is beta glucan… . In this study, we report that tumor-bearing mice treated with a combination of beta-glucan and anti-tumor mAb show almost complete cessation of tumor growth. …These results are important inasmuch as beta-glucan, an agent without evident toxicity, may be used to amplify tumor cell killing and may open new opportunities in the immunotherapy of cancer.”

Monoclonal Antibodies and Beta Glucan: Yan J, Allendorf DJ, Brandley B, “Yeast whole glucan particle (WGP) beta-glucan in conjunction with antitumour monoclonal antibodies to treat cancer.” Expert Opin Biol Ther; 5(5):691-702; James Graham Brown Cancer Ctr, Louisville, KY, 2005. Quote: “Extensive studies in preclinical animal tumour models have demonstrated the efficacy of combined oral particulate yeast beta-glucan with antitumour mAb [monoclonal antibodies] in terms of tumour regression and long-term survival. It is proposed that the addition of beta-glucan will further improve the clinical therapeutic efficacy of antitumour mAbs in cancer patients.”

Monoclonal Antibodies and Beta Glucan Hong F, Yan J, Baran J, Allendorf D, et al, “Mechanism by Which Orally Administered beta-1,3-glucans Enhance the Tumoricidal Activity of Antitumor Monoclonal Antibodies in Murine Tumor Models,” J Immunol, 173(2), 797-806, PMID: 15240666, Jul 15 2004. Quote: “Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast beta-1,3;1,6-glucan functions as an adjuvant for antitumor mAb…Orally administered beta 1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan fragments that were taken up by the CR3 [receptors] of marginated granulocytes. These granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb.”

Monoclonal Antibodies and Beta Glucan Hong F, Yan J, Baran J, Allendorf D, et al, “Beta-glucan Functions as an Adjuvant for Monoclonal Antibody Immunotherapy by Recruiting Tumoricidal Granulocytes as Killer Cells,” Cancer Res,, 63(24), 9023-31, PMID: 14695221, Dec 15 2003. Quote: “Previous studies suggested that i.v. beta-glucan might function as an adjuvant for antitumor mAbs. Glucan had been shown to function via the iC3b-receptor complement receptor 3 (CR3;CD11b/CD1B) thereby enhancing leukocyte killing of tumor cells coated with iC3b via naturally occurring antitumor antibodies. …These data suggest that the therapeutic efficacy of mAbs known to activate complement …could be significantly enhanced if they were combined with beta-glucan.”

Mouth Ulcers – Aphthous stomatitis: Koray M, Ak G, et al, “The effect of beta-glucan on recurrent aphthous stomatitis [Mouth Ulcers},” Alter Com0oement Med, 15(2)111-112, WMD 2009.

MRSA – Vaccine Adjuvant – Bacterial Infections: Paterson MJ, Caldera JR, Nguven C, Sharma P, Castro AM, et al, “Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy,” PLoS Pathog, 16(8):c1008733, PMID: 328177694, DOI: 10.1371/journal.ppat.1008733, Aug 20 2020. Quote: “Staphylococcus aureus (S. aureus) is one of the most common bacterial infections worldwide, and antibiotic resistant strains such as Methicillin-Resistant S. aureus (MRSA) are a major threat and burden to public health. We generated glucan particles [Beta 1,3/1,6 glucan] loaded with the four aureus proteins … . Vaccination of mice …promoted protection in a systemic model of S. aureus infection with a significant reduction on the bacterial burden in the spleen and kidneys. …This work suggests that the GP [glucan particle] vaccine system has potential as a novel approach to developing vaccines for S. aureus.”

Muscular Dystrophy – Duchenne: Brogi L, Marchese M, Cellerino A, et al, “B-Glucans as Dietary Supplement to Improve Locomotion and Mitochondrial Respiration in a Model of Duchenne Muscular Dystrophy,” Nutrients, 13(5):1619, PMID: 34065946, https://doi.org/10.3390/nu13051619, May 12, 2021. Quote: “Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration. B-glucans can modulate immune function by modifying the phagocytic activity of immunocompetent cells, notably macrophages. …The effects of 1,3-1,6 B-glucans showed that the incidence of dystrophic phenotypes was reduced. …Moreover, …1,3-1,6 B-glucans improve locomotor performances and mitochondrial function in dystrophic zebrafish. Therefore, for ameliorating their life quality, 1,3-1,6 B-glucans look like a promising diet supplement for DMD [Duchenne muscular dystrophy] patients… .”

Mucosal Immunity-Digestive Tract: Tsukada C, Yokoyama H, et al: “Immunopotentiation of intraepithelial lymphocytes in the intestine by oral administrations of beta-glucan,” Cell Immunol; 221(1):1-5 PMID 12742376; Jan 2003. Quote: “These results suggest that beta-glucan may be an important potentiator for mucosal immunity in the digestive tract.” Note: orally administered in mice in the study

Multiple Schlerosis – See Auto-Immune Disorders

Murine babesiosis: Benach J.L., et al., “Glucan as an adjuvant for a murine Babesia microti immunization trial,” Infection and Immunity, 35(3):947-951. 1982. Quote: “These observations demonstrate that glucan is an effective adjuvant in enhancing immunity to murine babesiosis.”

Murinehemopoietic cell proliferation: Niskanen E.O., Burgaleta C., Cline M.J., Goide D.W.; Effect of glucan, a macrophage activator, on murine hemopoietic cell proliferation in diffusion chambers in mice; Cancer Res 38: 1406-1409, 1978.

Mycobacterium Tuberculosis: Moorlag SJCFM, Khan N, Novakovimyelopoic B, “B-Glucan Induces Protective Trained Immunity Against Mycobacterium Tuberculosis Infection: A Key Role for IL-1,” Cell Rep. 19;31(7):107634. doi: 10.1016/j.celrep.2020.107634; PMID: 32433977, May 19 2020. Quote: “B-glucan is a potent inducer of epigenetic and functional reprogramming of innate immune cells, a process called “trained immunity,” resulting in an enhanced host response against secondary infections. …Mice treated with B-glucan are significantly protected against pulmonary Mtab [Mycobacterium tuberculosis] infection, which is associated with the expansion of hematopoietic stem and progenitor cells in the bone marrow and increased myelopoiesis. The administration of B-glucan may be used as a novel strategy in the treatment of mycobacterial infections and possibly as an adjuvant to improve anti-tuberculosis vaccines. Note: “myelopoiesis” refers to production of bo

Mycobacterium Bovis-Tuberculosis– Hetland G, et al. “Protective effect of beta-glucan against mycobacterium bovis, BCG infection in BALB/c mice.” Scand J Immunol, ;47(6):548-53; PMID 9652822 Jun1998. Quote: “There was a dose-dependent effect of beta-glucan injected before [Mycobacterium bovis,] BCG challenge on the number of BCG bacilli found in spleen and liver homogenates. In addition, antibody cross-reactivity was demonstrated between M. tuberculosis cell wall and beta-glucan. The results suggest that beta-glucan has a protective effect against M. bovis, BCG infection in susceptible mice.” [Note: Mycobacterium bovis, is a slow-aerobic bacterium and the causative agent of tuberculosis known as Bovine TB, which can also jump the species barrier from cattle and cause tuberculosis in humans and other mammals.]

Mycobacterium T – Tuberculosis: Hetland G, Sandven P; “Beta-1,3-Glucan reduces growth of Mycobacterium tuberculosis in macrophage cultures,” FEMS Immunol Med Microbiol 25;33(1):41-5. Mar 2002. Quote: “The results indicate that beta-glucans inhibit growth of M. tuberculosis in host cells in vitro, probably due to cellular stimulation and/or competitive inhibition of uptake of bacteria via CR3 (CD11b/18).”

Myeloid-derived suppressor cells – Oral Squamous Cell Carcinoma Cancer: Lo Y-W, Lee Alan Y-L, et al, “B-glucan therapy converts the inhibition of myeloid-derived suppressor cells in oral cancer patients, “ Oral Diseases, https://doi.org/10.1111/odi.13827 , March 3 2021, Quote: “Preoperative administration of B-glucan can augment anti-tumor immunity and increase RFS [recurrence-free-survival] rate via subversion of suppressive function of MDSC [Myeloid-derived suppressor cells] in OSCC [oral squamous cell carcinoma] patients].” Note: Myeloid-derived suppressor cells [MDSCs] are a group of immune cells from a family of cells that originate from bone marrow stem cells. MDSCs expand disease situations such as chronic infections and cancer caused by altered formation of blood cells.

Mycotoxins – see Fungal Defense and Fungus also

Mycotoxins-fumonism: El-Naggar, et al. “Evaluation of B-D-glucan biopolymer as a novel mycotoxin binder for fumonisin and deoxynivalenol in soybean feed.” Foodborne Pathog Dis. (6):433-8, PMID 24660841 Jun 11 2014. Quote: “…This study aimed to evaluate the β-D-glucan biopolymers as a mycotoxin binder for fumonisin (FUM) and deoxynivalenol (DON) toxins as well as their effect on the nutritional value of soybean, which is considered one of the important feed row materials. …this study found a new approach to reduce Fusarium mycotoxins in feed to an allowable safe limit and at the same time maintaining the nutritional value of these materials.”

Mycotoxins – Environmental Toxins – Vetvicka V, “Effects of B-glucan on some environmental toxins: An overview.” Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub; ;158(1):1-4. PMD: 24399292. 2014. Quote: “…glucan reduces the immunosuppressive effects of a number of agents including chemo therapy and radiation. … An overview of the effects of glucan on the mycotoxin, aflotoxin and other environmental toxins (mercury-thimerosal, depleted uranium). Glucan is effective as a natural immunomodulator and could be used as an inexpensive solution to reducing the adverse effects of some environmental toxins.”

Mycotoxins – see Fungus also – Hunter KW, Jr. Berner MD, Sura ME Alvea BN, “IFN-gamma primes macrophages for enhanced TNF-alpha expression in response to stimulatory and non-stimulatory amounts of microparticulate beta-glucan.,” Immunol Lett ; 15:98(1): 115-22. Department of Microbiology and Immunology, University of Nevada School of Medicine, Applied Research Facility, MS-199, Reno, NV 89557, USA. April 2005, Quote: …”we have tested a new microparticulate form of beta-(1–> 3)-D-glucan (MG) from Saccharomyces cerevisiae for its ability to induce proinflammatory cytokine secretion in mouse peritoneal macrophages in vitro, and we have examined the effect of IFN-gamma. MG was rapidly phagocytized by peritoneal macrophages, and these MG-treated macrophages upregulated TNF-alpha, IL-6, and IL-1beta mRNAs and secreted these proinflammatory cytokines. These data suggest that a synergy between IFN-gamma and beta-glucan may have evolved to lower the threshold of sensitivity of the innate immune response to fungal pathogens.” [respond faster in attacking fungal pathogens – mycotoxins]

Myocardial Injury/Cardioprotective: Cetin E, “Pretreatment with B-glucan attenuates isoproterenol-induced myocardial injury in rats,” Exp Physiol, doi: 10.1113/EP086739, PMID: 30677174, Jan 24, 2019. Quote: “This study was designed to investigate the cardioprotective effect of pretreatment with B-glucan,…from Saccharomyces cerevisiae, against isoproterenol (ISO)-induced myocardial injury… . The oral pretreatment of B-glucan prevented almost all parameters of isooproterenol induced myocardial injury in rats.”

See also “Heart” and “Cardio” classifications

N

Nanoparticles and Nanomaterials (see also Micronization) [Note: 1,000 nanos equals 1.0 micron or 1.0 nano equals .001 microns.].

Nanoparticles – Beta Glucan – Jialu X, Me Q, et al, “Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth [mouse studies],” Nature Communications, 13110, https://doi.org/10.1035/s41467-021-27750-21 , Jan 10 2022. Quote, “Intriguingly, the induction anti-cancer immunity appears to inversely correlate with the size of nanoparticles. Small size …showed better efficiency in controlling tumor growth after intratumor injection compared with middle and large size of YC NPs.”

Nanoparticles – Beta Glucan Vaccine Adjuvant: Colaco M, Costa JP, Borges O, “Glucan Particles: Choosing the Appropriate Size to Use as a Vaccine Adjuvant”, Methods Mol Biol, 2022:2412:269-280, PMID: 34918250, https://doi.org/10.1007/98-1-0716-1892-9.13 , Dec 17, 2021. Quote: “Beta-glucans are a group of polysaccharides with intrinsic immunostimulatory properties which makes the design of new particulate vaccine adjuvants based on B-glucans very promising. The size of the particles and the antigen loading method, encapsulated into particles or absorbed on its surface, will influence the toxicological and adjuvanticity properties of the particulate adjuvant. Herein we describe the production of glucan nanoparticles (NPs) with three different sizes, approximately 150 nm [0.15 microns], 350 nm [0.35 microns], and microparticles as shells (GPs) with approximately 3 um [3.0 microns]. The association of the antigen to the particulate adjuvant is described using model protein antigens. The method can be easily adapted for real protein antigens.”

Nanoparticles – Cancer – Breast – B-Glucan: Parthasarathy R, Kumar SP, et al, “Synthesis of B-Glucan Nanoparticles from Red Algae-Derived B-Glucan for potential Biomedical Applications,” Appl Biochem Biotechnol, PMID: 34542823, https://doi.org/10.1007/s12010-021-03674-x , Sep 20 2021. Quote: “Hence, the study reports that the B-GLuNPs [B-Glucan nanoparticles] have a potential to be used as a promising alternative drug against human breast cancer.”

Nanoparticles – Gene Delivery System: Kyungwoo L, Min D, et al, “Self-Assembling B-Glucan Nanomedicine for the Delivery of siRNA [small interfering RNA],” Biomedicines, 8(11);E497, PMID: 33198404, https://doi.org/10.3390/biomedicines8110497, Nov 12 2020. Quote: “We aimed to design and manufacture a transporter capable of delivering small interfering RNAs (siRNAs) into the skin without causing any damage. B-glucans are unique chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability. …In this study, B-glucan nanoparticles were designed and manufactured to deliver genetic material to the target cells. The B-glucan molecules were self-assembled with an siRNA into nanoparticles of 300-400 nm in diameter via a conformational transition process, in order to construct a gene delivery system. The assembled gene nanocarriers were associated with high gene-loading ability. …Our results provide evidence that B-glucan nanoparticles can be effectively used to deliver siRNA [small interfering RNA] into the cells.”

Nanoparticles -Carrier Composite (Doxorubicin): Huang J, Wu C, et al, “Chiral Active B-Glucan Nanoparticles for Synergistic Delivery of Doxorubicin and Immune Potentiation,” Int J Nanomedicine, 15-5083-5095, PMID: 32764938, https://doi.org/10.2147/UN.525814-5, Jul 14 2020. Quote: “B-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified. ….B-glucan nanoparticles can activate macrophages to produce immune enhancing cytokines (IL-1B, IL-6, TNF-alpha, IFN-y). This work demonstrates that B-glucans nanoparticles with special chiral feature which leading to strong immunopotentiation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer treatment.”

Nanomaterials – Beta Glucan: Xiaojie L, Cheung PCK, “Application of natural B-glucans as biocompatible functional nanomaterials,” Food Science and Human Wellness, Vol 8, Issue 4, Pp 315-319, doi.org/10.1016/j.fshw.2019.11.005, Dec 2019. Quote: “B-glucans have been known as functional foods since they are capable of boosting both the innate and adaptive immune systems, thus modulating the immunological responses against cancer, bacteria, viruses and inflammation. …B-glucans from yeast also have a capacity to stimulate immune responses to suppress the chronic inflammation in diabetic mice. …B-glucans are natural bio-materials having the potential to form stable nano-hybrids with excellent bio-pharmaceutical properties to be orally administrated for therapeutic cancer treatment. …Furthermore, no obvious harmful side effect of these nano-hybrids was evident by histological analysis of major organs in treated mice.”

Nanoparticles: Farris E, Brown DM, Ramer-ETait, Pannnier AK, “Miro-and nanoparticulates for DNA vaccine delivery” Exp Biol Med (Maywood) pii:1535370216643771; PMID: 27048557; April 4, 2016. Quote: “In contrast, nanoparticle encapsulation leads to increased internalization, overall greater transfection efficiency, and the ability to increase uptake across mucosal surfaces. Moreover, selection of the appropriate biomaterial can lead to increased immune stimulation and activation through triggering innate immune response receptors and target DNA to professional antigen presenting cells. Finally, the selection of materials with the appropriate properties to achieve efficient delivery through administration routes conducive to high patient compliance and capable of generating systemic and local (i.e. mucosal) immunity can lead to more effective humoral and cellular protective immune responses.”

Nanoparticles -Beta Glucan: Soto ER, Caras AC, et al, “Glucan Particles for Macrophage Targeted Delivery of Nanoparticles,” J Drug Daily, 143524, PMID 22013535, Oct 13, 2011. Quote: Glucan particles (GPs) are hollow, porous 2-4 micron microspheres derive from the cell walls of Baker’s yeast (Saccharomyces cerevisiae). The 1,3-B-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing B-glucan receptors.”

Nanoparticles – Micronization [1,000 Nanos = 1 Micron] : Size: Zhang M, Kim Julian, et al, “Optimizing Tumor Microenvironment for Cancer Immunotherapy: B-Glucan-Based Nanoparticles,” Front Immunol, 9:341, PMC5834761, https://doi.org/10.3389/fimmu.2018.00341. PMID: 29535722. Feb 26 2018. Quote: “This article reviews the development of B-glucan and B-glucan-based nanoparticles as immune modulators of tumor microenvironment (TME). …we discuss the mechanisms of conditioning tumor microenvironment (TME) using B-glucan and B-glucan-based nanoparticles, and how this strategy enables future design of optimal combination cancer immunotherapies. …A particulate B-glucans derived from yeast mediates antitumor immune responses by inducing pro-inflammatory cytokine secretion and stimulating innate immune effector cell activation.”

Nanomedicine – Micronization [1,000 Nanos = 1 Micron] Malinoski FJ, “The nanomedicines alliance: an industry perspective on nanomedicines,” NanoMedicine 10(8): 1819-20, PMID 25038497, Nov 2014. Quote: “The field of nanomedicines has expanded significantly in recent years in the breadth of compounds under development … .”

Nanomedicine – Cancer – Colon – Chen J, et al, “The application of fungal B-glucans for the treatment of colon cancer.” Anticancer Agents Med Chem, 13(5):725-30. PMID:23293888 Jun 2013. Quote: “Evidence has supported the idea that beta-glucans can decrease the size of xenografted colon cancer tumors via the stimulation of the immune system and direct cytotoxicity. Beta-glucans can also have synergistic effects with chemotherapeutic agents and other immune stimulators, and an innovative strategy is to use beta-glucans to deliver nanoparticles containing chemotherapeutic agents to the site of the colon cancer and, thus, improve the therapeutic efficacy.”

NSAID – Indomethacin: Takahashi H, Ohno N, et al, “Association of immunological disorders in lethal side effect of NSAIDs [indomethacin-not ibuprofen or nabmetone] on beta-glucan-administered mice,” FEMS Immunol Med Microbiol, 31(1):1-14, PMID: 11476975, https://doi.org/10.1111/j.1574-695X.2001.tb0159.x, WMD, Jul 2001.

Nasal Discharge – Soar Throat – Respiratory Tract Infection-Clinical Human Trial: Mah E, Kaden VN, Kelley KM, Liska DP, “Soluble and Insoluble Yeast B-Glucan Differentially Affect Upper Respiratory Tract Infection in Marathon Runners: A Double-Blind, Randomized Placebo-Controlled Trial,” J Med Food, https://doi.org/10.1089/jmf.2019.0076, PMID: 31573387, Oct 1 2019. Quote: “…Total severity of URTI [Upper Respiratory Tract Infection] was significantly lower in the insoluble yeast B-glucan group compared to the placebo group. …Severity ratings for nasal discharge was significantly lower in both the insoluble and soluble yeast B-glucan groups compared to the placebo groups. …severity rating for sore throat was lower in the insoluble, but not the soluble yeast B-glucan group compared to the placebo group. …The insoluble yeast B-glucan group, but not the soluble yeast B-glucan group also reported fewer URTI symptomatic days compared to the placebo group.”

Natural Killer (NK) Immune Cells-Clinical Human Trial: Lee YJ, Paik DJ, et al, “Agrobacterium sp.-derived B-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study.” Nutr Res Pract, Feb 11(1) 43-50. PMID: 28194264; Feb 2017; Quote: “The results showed that supplementation with bacterial β-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of β-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.”

Nephropathy-Contrast Induced (Acute Renal Failure): Koc E, Reis KA, Ebinc FA, Pasaoglu H, Demirtas C, Omeroglu S, Derici UB, Erten Y, Bali M Arinsov T, Sindel S; “Protective effect of beta-glucan on contrast induced-nephropathy [acute renal failure] and a comparison of beta-glucan with nebivolol and N-acetylcysteine in rats.” Dept of Nephrology, Ankara, Turkey; Clin Exp Nephrol, Apr 26 2011. Quote: “…beta-glucan (BG), which has antioxidant and immunomodulatory effects, attenuates renal ischemia-reperfusion injury. …This study suggest that BG protects or ameliorates against contrast-induced nephropathy.”

Neoplasia: Proctor and Yamamura; “Letters to the Editor: Effectiveness of Glucan in the Treatment of Human Neoplasia”. J. Nat’l Cancer Inst.; 61: 1179-1180. 1978.

Neoplasia: Schultz, et al., in “Immune Modulation and Control of Neoplasia by Adjuvant Therapy”, Chirigos, ed., Raven Press, New York; pp. 241-248. 1978.

Neoplastic Diseases: DiLuzio N.R. (deceased), Williams D.L., Browder I.W.; Soluble phosphorylated glucan: methods and compositions for treatment of neoplastic diseases; U.S. Patent 4818752; 1989.

Neurodegenerative Diseases – Beta Glucan: Ciecierska A, Drywien ME, et al, “Nutraceutical functions of beta-glucans in human nutrition,” Rocz Panstw Zakl Hig, [Translation: Roczniki Panstwowego Zakladu Higieny, Responsiveness to the hospital patient needs in Poland], 70(4):315-324, (ISSN: 0035-7715), 2019. Quote: “Beta-glucan[s]…are attributed a number of beneficial health properties, including the prevention and treatment of certain digestive diseases and supporting the immune system. …Beta-glucan reduces cholesterol and glucose concentrations in the blood, which reduces the risk of cardiovascular disease and diabetes. …beta-glucan also exhibits antioxidant properties by scavenging reactive oxygen species, thereby reducing the risk of diseases, including atherosclerosis, cardiovascular diseases, neurodegenerative diseases, diabetes, and cancer. Immunostimulatory and antitumor effects have also been reported. …Beta-glucan belongs to the group of prebiotics which stimulate the growth and activity of the desired natural intestinal microbiota, while inhibiting the growth of pathogens. …Such a number of health benefits resulting from the properties of beta-glucan may play a key role in improving health benefits resulting from the properties of beta-glucan and preventing chronic non-communicable diseases, such as diabetes, hypercholesterolemia, obesity, cardiovascular diseases, and cancer.

Neurologic Health-Brain Function: Nelson ED, Ramberg, JE, “Neurologic effects of exogenous saccharides: a review of controlled human, animal, and in vitro studies.” Nutr Neurosci, 15(4):149-162, WMD, PMID 22417773; DOI: 10.1179/1476830512Y.0000000004, Feb 10, 2012. Quote: “…the literature suggests that certain naturally occurring compounds and polysaccharide-rich extracts [including beta glucan] show promise, when taken orally, in supporting neurologic health and function.”

Neutropenia and Lymphopenia: Sima P, et al, “Effects of glucan on bone marrow.” Ann Transl Med. (2)18. PMC 4202472 Feb 2, 2014. Quote: “The extensive research studying various effects of glucans on bone marrow showed significant restoration of both lymphopenia and neutropenia. … glucan might be widely used as radioprotectant that could mitigate the biological effects of radiation exposure both in cases of radiation accidents or in medically used irradiation.”

Neutrophils – Tumors – Zou S, Duan B, Xu X, “Inhibition of tumor growth by B-glucans through promoting CD4+ T cell immunomodulation and neutrophil-killing in mice.” Carbohydr Polym, 213:370-381, PMID: 30879681, Jun 1 2019. Quote: “It was proposed that B-glucans promoted CD4+ T cell immunomodulation and neutrophils infiltration into tumors, leading to tumor growth inhibition. These findings reveal that B-glucans can be used as an effective agent for cancer immunotherapy.”

Nitric Oxide Synthesis: Ohno N, et al; “Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophages in mice;” Biol. Pharm. Bull. 19:608-612; 1996.

Nitric Oxide: , Hunter Jr. KW, Gault R, Jordan F, “Mode of Action of B-Glucan Immunopotentiators,” Department of Microbiology, University of Nevada School of Medicine, Oct 1998. Quote: “…these data do indicate Glucan particle size is an important factor in the production of nitric oxide. Nitric oxide is generated during the “oxidative burst” that kills ingested microbes [bacteria, viruses, fungi, parasites, etc]. This would suggest that the small particle glucan has greater ability to enhance the immune system than the globular form of glucan.”

Non-alcoholic Dectin-1 – fatty liver disease (NAFLD): Wang Min-xlu, Luo Wu, Ye Lin et al, “Dectin-1 plays a deleterious [harmful] role in high fat diet-induced NAFLD [non-alcoholic fatty liver disease] of mice through enhancing macrophage activation,” Acta Pharmacologica Sinica 120-132, June 10, 2022. Quote: “Dectin-1 was required for hepatic macrophage activation and inflammatory factor induction. …Condition media generated from Dectin-1 deficient macrophages failed to cause hepatocyte lipid accumulation and hepatic stellate activation. …[No Dectin-1 no activation] Dectin-1 in NAFLD through enhancing macrophage pro-inflammatory responses and suggest that it can be targeted to prevent inflammatory NAFLD.”

NSAIDS and Beta Glucan: Takahasi H, et al, “Association of immunological disorders in lethal side effects of NSAIDS on B-glucan-administered mice.” FEMS Immunol. Med. Microbiol., 31, 1-14, . PMID: 476975 2001. Quote: “…gastrointestinal damage by NSAIDs was more severe in beta-glucan-administered mice, resulting in peritonitis by enteric bacteria …”

Nuclear Emergency: “The Biological activity of beta-glucans”; Minerva Medical; 100(3):237-245; Pub Med 19571787; Jun 2009; Quote: “…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].”

Obesity

Obesity – Beta Glucan / Silymarin-milk thistle: Filho V, SantamalinaAB, et, “Novel nutraceutical supplements with yeast B-glucan, prebiotics, minerals, and silybum marianum (silymarin/milk thistle) ameliorate obesity-related metabolic and clinical parameters: A double-blind randomized trial.” Randomized Controlled Trial – Front Endocrinol (Lausanne); 13:1089938, PMID: 36778595, https://doi.org/10.3389/fendo.2022.1089938 . Jan 27, 2023. Quote: “The WHO estimates the worldwide prevalence of 1.9 billion overweight adults and more than 650 million people with obesity. These alarming data highlight the high and growing prevalence of obesity and represent a risk factor for the development and aggravation of other chronic disease, such as nonalcoholic fatty liver disease (NAFLD) that is frequently considered the hepatic outcome of type 2 diabetes. …In a condition associated with sedentary and no nutritional intervention, the new nutraceutical supplement composition demonstrated the ability to be a strong …tool to improve important biomarkers associated with obesity and its comorbidities.”

Obesity – Beta Glucan: Mo X, Sun Y, Liang X, et al, “Insoluble yeast B-glucan attenuates high-fat diet-induced obesity by regulating gut microbiota and its metabolites,” Carbohydr Polym 281:119046, PMID: 35074119, https://doi.org/10.1016/j.carbpol.2021.119046 April 1, 2022. Quote: “ After 24 weeks of long-term supplementation, IYG [insoluble yeast B-glucan] ameliorated [reduced] weight gain, dyslipidemia, systemic inflammation, glucose intolerance and insulin resistance in high-fat diet [HFD]. In addition, HFD induced gut dysbiosis and changed levels of short-chain fatty acids and lipopolysaccharide were restored by IYG [insoluble yeast B-glucan]. iYG also mitigated HFD induced colonic inflammation and oxidative stress. …elevated gut permeability was recovered by insoluble yeast B-glucan [IYG]. This study demonstrated that insoluble yeast B-glucan [IYG], as a potential prebiotic, exhibited a protective effect on high fat diet [HFD] induced obesity.”

Obesity – Beta Glucan: So Sik Yu, Wu Qinglong, et al, “Yeast B-glucan reduces obesity-associated Bilophila abundance and modulates bile acid metabolism in healthy and high-fat diet mouse models,” Am J Physil Gastrointest Liver Physiol 321(6):G639-G655, PMID: 34643089, https://doi.org/10.1152/aipgi.00226.2021 , Dec 1, 2021. Quote: “Our results demonstrate that Y-BG [yeast beta glucan] modulates gut microbiota community composition and bile acid signaling,…Yeast-beta glucan [Y-BG] improved insulin sensitization ..and reduced Bilophila abundance.” Note: Bilophila wadsworthia synergizes with high-fat diet to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis.

Obesity – Beta Glucan: Vlassopoulou M, Yannakooulia M, et al, “Effects of fungal beta-glucans on health – s systematic review of randomized controlled trials,” Food Funct,PMID: 33876798, https://doi.org/10.1039/d1fo00122a, Mar 31, 2021. Quote: “Thirty-four RCTs [randomized controlled trials] … are included in the present review. The primary physiological outcome of the majority of the interventions was immunomodulation, which resulted in (a) strengthened immune defense that reduces the incidence and symptoms of cold, flu and other respiratory infections and (b) improvement of allergic symptoms. …the cohorts that received the polysaccharides of interest reported improvement in their mood states as well as amelioration of overall wellbeing. …it might also be useful as a complementary agent to patients undergoing cancer therapies. Furthermore, supplements containing beta-1,3/1,6-d-glucan administered to overweight/obese adults might have the potential to decrease comorbid [additional] conditions associated with obesity. Notably, no adverse event causally related to glucans was recorded.”

Obesity – Heart – Cardiovascular Disease: Wouk J, Dekker RFH, Queiroz, et al, “B-Glucans as a panacea for a healthy heart? Their roles in preventing and treating cardiovascular diseases,” Int J Biol Macromol, 17:80141-8130(21)00366-4. PMID: 33609583, https://doi.org/10.1016/j.ijbiomac.2021.02.087 , Feb 2021. Quote: “The B-glucans from all of the sources cited demonstrated potential hypoglycemic, hypocholesterolemic and anti-obesogenicity activities, reduced hypertension and ameliorated the atherosclerosis condition. More recently, B-glucans are recognized as possessing prebiotic properties that modulate the gut microbiome and impact on the health benefits including cardiovascular. Overall, all the studies investigated unequivocally demonstrated the dietary benefits of consuming B-glucans regardless of source, thus constituting a promising panaceutical approach to reduce CVD risk factors. …[Summary in study]: β-Glucans decrease aggregation of atherosclerotic plaque, size and secretion. Both systolic and diastolic blood pressure are reduced after intake of β-glucan. [and] β-Glucans reduce oxidative stress preventing & ameliorating cardiovascular diseases.”

Obesity -Beta Glucan: Cordero JG, Ruiz BS, et al, “Effectiveness of hydroxycinamates and beta-glucans as dietary tools against obesity and its associated dysfunctions, and their application as nutraceuticals,” Nutr Hosp, Vol 37, Num 5, pp 887-1092, PMID: 32960625, DOI: 10.20960/nh.031125, Sep 22 2020. Quote: Obesity has been related to disorders such as type-2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, among others, which has made of obesity the second cause of preventable death, only behind smoking. Among bioactive compounds, this study will focus on B-glucans, … and hydroxycinnamic acids, …compounds show complex and multifactorial effects, acting as hypolipemic, hypoglycemic, antioxidant, prebiotic and satiating agents. They act by modulating different metabolic pathways, affecting the absorption and metabolism of lipids and carbohydrates, reducing oxidative damage, promoting the proliferation of beneficial bacterial species, and reducing dietary intake.. It may be concluded that …beta-glucans …have potential as a nutritional tool for management of obesity and associated metabolic dysfunctions.” Note: Research in Spanish

Obesity -Beta Glucan: Ciecierska A, Drywien ME, et al, “Nutraceutical functions of beta-glucans in human nutrition,” Rocz Panstw Zakl Hig, [Translation: Roczniki Panstwowego Zakladu Higieny, Responsiveness to the hospital patient needs in Poland], 70(4):315-324, (ISSN: 0035-7715), 2019. Quote: “Beta-glucan[s]…are attributed a number of beneficial health properties, including the prevention and treatment of certain digestive diseases and supporting the immune system. …Beta-glucan reduces cholesterol and glucose concentrations in the blood, which reduces the risk of cardiovascular disease and diabetes. …beta-glucan also exhibits antioxidant properties by scavenging reactive oxygen species, thereby reducing the risk of diseases, including atherosclerosis, cardiovascular diseases, neurodegenerative diseases, diabetes, and cancer. Immunostimulatory and antitumor effects have also been reported. …Beta-glucan belongs to the group of prebiotics which stimulate the growth and activity of the desired natural intestinal microbiota, while inhibiting the growth of pathogens. …Such a number of health benefits resulting from the properties of beta-glucan may play a key role in improving health and preventing chronic non-communicable diseases, such as diabetes, hypercholesterolemia, obesity, cardiovascular diseases, and cancer.

Obesity – metabolic stress: Muthuramalingam K, Singh V, et al, “Dietary intervention using (1,3)/(1,6)-B-glucan, a fungus-derived soluble prebiotic ameliorates high-fat diet-induced metabolic distress and alters beneficially the gut microbiota in mice model,” Eur J Nutr, doi: 10.1007/s0394-019-021, Pubmed: 31664519, Oct 29 2019. Quote: “B-glucan consumption exhibited anti-obesity property in mice groups fed with HFD [High Fat Diet]. In addition, B-glucan ameliorated HFD-induced hepatic stress, colonic motility and intestinal atrophy (reduction in colon length, goblet cells, and mucosal layer thickness). Further, B-glucan incorporation shifted bacterial community by increasing butyrate-producing bacteria such as Anaerostipes, Coprobacillus, and Roseburia and decreasing reportedly obesity-associated bacteria such as Parabacteroides and Lactococcus.”

Obesity: Kim IS, Lee SH, et al, “Oral Administration of B-Glucan and Lactobacillus plantarum Alleviates Atoopic Dermatitis-like Symptoms,” J Microbiol Biotechnol, doi: 10.4014/jmb.1907.07011. PMID 31546298, Sep 9 2019. Quote: “These findings suggest that the dietary supplementation of B-1,3/1,6-glucan and/or L. plantarum LM1004 has a great potential for treatment of Atopic dermatitis (AD) as well as obesity in humans through mechanisms that might involve modulation of host immune systems and gut microbiota.”

Obesity: Bordoni A, Boesch C, et al, “The role of bioactives in energy metabolism and metabolic syndrome,” Proc Nutr Soc, 78(3):340-350, PMID 30967168, Aug 2019. Quote: “Some food bioactives potentially exert anti-obesity effects. Anthocyanins (ACN), catechins, B-glucan (BG) …are among the most promising candidates and have been considered as a strategy for the development of functional foods counteracting body weight gain. …Abdominal obesity is an important criterion for metabolic syndrome (MetS) diagnosis along with glucose intolerance, dyslipidemia and hypertension. ” Note: Metabolic syndrome is often described as “pre-diabetes.”

Obesity: Maheshwari G, Sowrerajan S, et al, “B-Glucan, a dietary fiber in effective prevention of lifestyle diseases – An insight,” Bioactive Carb. and Dietary Fibre, Vol 19, DOI: 10.1016/j.bcdf.2019.100187, July 2019. “Quote: “B-Glucan (B-G), a dietary fiber and a biologically active natural polysaccharide, is helpful in the prevention and control of obesity, cardiovascular disease, diabetics and cancer. …Lowering the LDL cholesterol, the glycemic index and blood sugar, along with the antioxidant, anticancer and free radical scavenging property, B-glucan is efficient in trapping the reactive oxygen.”

Obesity-Human Clinical Studies Review: Bashir KMI, Choi JS, “Clinical and Physiological Perspectives of B-Glucans: The Past, Present, and Future,” Int J Mol Sci, 18(9) PMID: 28872611, Sep 5 2017, Quote: “B-Glucans are a group of biologically-active fibers or polysaccharides from natural sources with proven medical significance. B-Glucans are known to have antitumor, anti-inflammatory, anti-obesity, anti-allergic, anti-osteoporotic and immunomodulating activities. …The medical significance and efficiency of B-glucans are confirmed in vitro, as well as using animal- and human-based clinical studies.”

Obesity – Weight Gain-Human Clinical Trial: Mosikannon K, Arthan D, et al,“Yeast B-Glucan Modulates Inflammation and Waist Circumference in Overweight and Obese Subjects,” J Diet Suppl, WMD, https://doi.org/10.1080/19390211.2016.1207005; PMID 27715351, Mar 4, 2017: Quote: “A randomized, double blinded, placebo-controlled, clinical trial design enrolled 44 overweight/obese participants with body mass index ≥23 kg/m2. Supplementation of yeast β-glucan for six weeks modulated pro-cytokines that accelerate overweight/obese comorbidities [multiple health issues] and reduced blood pressure as well as waist circumference, the strong risk factors for cardiovascular disease, in overweight/obese subjects. Thus, β-glucan might have the potential to decrease comorbid conditions associated with overweight/ obesity. …B-glucan increased interleukin-10 (IL-10), an anti-inflammatory cytokine, by 23.97% from baseline at week two compared with controls and 31.2% at week six …B-glucan reduced pro-inflammatory cytokines IL-6 at week six and tumor necrosis factor-a at week two compared to controls. Note: “comorbid conditions” would be negative health issues contributed to or caused by overweight/obesity.

Obesity – Weight Loss-Human Clinical Trials Review: Steir H, Ebbeskotte V, Gruenwald J, “Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan,” Nutr J; 13;38, PMID 24774968, Apr 28, 2014. Quote: “…several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect. ,,,Further, numerous studies reported other health benefits of B-glucans, including hepatoprotective, wound healing, weight loss, antidiabetic and cholesterol lowering functions.”

Obesity and Diabetes: Khoury DE, Cuda C, et al, “Beta Glucan: Health Benefits in Obesity and Metabolic Syndrome,” J Nutr Metab, eoi: 10.1155/2012/851362 , PMID 22187640, Dec 11 2011. Quote: “In this particular study, chitin-glucan [Beta 1-3 branched chitin-glucan] decreased high fat-induced body weight gain, fat mass development, fasting hyperglycemia, glucose intolerance, hepatic triglyceride accumulation, and hypercholesterolemia, irrespective of caloric intake.”

Obesity and Diabetes: Nazare JA, Normand S, “Modulation of the postprandial phase by beta-glucan in overweight subjects: effects on glucose and insulin kinetics,”, Mol Nutr Food Res, 53(3):361-369, WMD, PMID: 1837474, DOI: 10.1002/mnfr.200800023, Mar 2009. Quote: “The addition of BG [beta-glucan] slowed the appearance of glucose in plasma, resulting in longer-lasting insulin secretion which exerted a prolonged inhibition of EGP [endogenous glucose production] and lipolysis.”

Organ Injury – Sepsis: Sener G, Toklu H, et al; “Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis,” Int Immunopharmacol:1387-96 Epub 2005/Aug 2005. Quote: “Sepsis leads to various organ damage and dysfunction. One of the underlying mechanisms is thought to be oxidative damage due to generation of free radicals. …Elevated plasma TNF-alpha levels in septic rats [was] significantly reduced to control levels in beta-glucan treated rats. Since beta-glucan administration reversed these oxidant responses, it seems likely that beta-glucan protects against sepsis-induced oxidative organ injury.”

Osteoclastogenesis – Bone Resorption: Hara S, Nagai-Yoshioka Y, et al, “Dectin-1-mediated suppression of RANKL-induced osteoclastogenesis by glucan from baker’s yeast,” Cell Physiol, PMID: 33305824, DOI: 10:1002/jcp.30217, Dec 11 2020. Quote: “Dectin-1 is a lectin receptor of B-glucan and is specifically expressed in osteoclast precursor cells. …glucan from baker’s yeast suppresses RANKL-induced osteoclastogenesis and can be applied as a new treatment strategy for bone-related diseases.” Note: “Osteoclastogenesis” refers to the development of osteoclasts from blood cells from monocytes/macrophages. Bone resorption is the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. “RANKL” is Receptor Activator of Nuclear factor Kappa-B Ligand; also known as tumor necrosis.

Osteoporosis: Bashir KMI, Choi JS, “Clinical and Physiological Perspectives of B-Glucans: The Past, Present, and Future,” Int J Mol Sci, 18(9) PMID: 28872611, Sep 5 2017. Quote: “B-Glucans are a group of biologically-active fibers or polysaccharides from natural sources with proven medical significance. B-Glucans are known to have antitumor, anti-inflammatory, anti-obesity, anti-allergic, anti-osteoporotic and immunomodulating activities. …The medical significance and efficiency of B-glucans are confirmed in vitro, as well as using animal- and human-based clinical studies.”

Oxidative Burst: Camili , Eren E, Williams DL, et al, “Impaired phagocytosis directs human monocyte activation in response to fungal derived B-glucan particles,” Eur J Immunol, 48(5):757-770, PMID 29313961. May 2018. Quote, “Recognition of the fungal cell wall carbohydrate B-glucan by the host receptor Dectin-1 elicits broad immunomodulatory responses, such as phagocytosis and activation of oxidative burst. These responses are essential for engulfing and killing fungal pathogens.”

Oxidative Stress

Oxidative Damage Reduction – anti-Obesity: Cordero JG, Ruiz BS, et al, “Effectiveness of hydroxycinamates and beta-glucans as dietary tools against obesity and its associated dysfunctions, and their application as nutraceuticals,” Nutr Hosp, Vol 37, Num 5, pp 887-1092, PMID: 32960625, DOI: 10.20960/nh.031125, Sep 22 2020. Quote: Obesity has been related to disorders such as type-2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, among others, which has made of obesity the second cause of preventable death, only behind smoking. Among bioactive compounds, this study will focus on B-glucans, … and hydroxycinnamic acids, …compounds show complex and multifactorial effects, acting as hypolipemic, hypoglycemic, antioxidant, prebiotic and satiating agents. They act by modulating different metabolic pathways, affecting the absorption and metabolism of lipids and carbohydrates, reducing oxidative damage, promoting the proliferation of beneficial bacterial species, and reducing dietary intake.. It may be concluded that …beta-glucans …have potential as a nutritional tool for management of obesity and associated metabolic dysfunctions.” Note: Research in Spanish

Oxidative Stress: Sugita P, Sargowo D, “Abstract 366: Beta-1,3/1,6-D-Glucan Chemical Structure Characterization of Indonesian Ganoderma lucidum Mycelium Extract,” Artheriosclerosis, Thrombosis and Vascular Biology (ATVB) Vol 39, Issue Suppl 1, July 19, 2019. Quote: “B-1,3/1,6-D-Glucan may act as an anti-inflammatory and oxidative stress suppressor which may result in the repair of cardiomyocytes and prevent ischemia.”

Oxidative Stress – Sepsis-Human Clinical Trials Review: Prauchner CA, “Oxidative stress in sepsis: Pathophysiological implications justifying antioxidant co-therapy;” Burns, pii:S0305-4179(16)30400-4. PMID 28034666; Dec 26, 2016. Quote: “Sepsis is one of the main causes of death among critically ill patients. Sepsis pathogenesis includes infection by gram-negative and gram-positive bacteria, fungi, or both; exacerbated inflammatory response; hypotension, with potential to cause vasodilatory shock; and lesser delivery of oxygen to tissues due to impairment of oxygen utilization by cells. Antioxidants could inhibit the over expression of iNOS [nitric oxide synthase] in sepsis. In line with this, several antioxidants such as vitamins C and E, polyphenols, melatonin, β-glucan, N-acetylcysteine, mitochondrion-targeted antioxidants (MitoQ, MitoE, and peptides associated with dimethyltyrosine), selenium salts, and organoselenium compounds were effective in ameliorating oxidative stress in animal models of sepsis and in a number of clinical trials with septic patients.”

Oxidative Stress, Sciatic Nerve, Brain: Harun Alp, Sefer Varol, et al, “Protective Effects of Beta Glucan and Gliclazide on Brain Tissue and Sciatic Nerve of Diabetic Rats Induced by Streptozosin,” Experimental Diabetes Res, Vol 2012, Article ID 23032, 2012. Quote: “Recent studies have reported that beta-glucans could reduce hyperglycemia, hyperlipidemis, and hypertension. …It was found that B-glucan is an antioxidant … . Therefore, beta-glucans have great potential for the treatment of diabetes and associated neurological diseases including diabetic neuropathy and encephalopathy. Thus, beta glucan can lead new approaches for the prevention of diabetic neurologic complications and vascular risk factors by reducing oxidative damage of this molecule. …

In addition, it has been suggested that beta-glucans may be used to prevent or treat excessive microglial activation during chronic inflammatory conditions. Gliclazide …is a second generation sulfonylurea hypoglycemic agent…gliclazide may contribute to the control of physiopathological mechanisms underlying both the process of aging and type 2 diabetes by reducing oxidant stress and DNA damage,… .In diabetic experimental models it has been reported that gliclazide potentially protects the vasculature through improvements in plasma lipids and platelet function. …This study results suggested that beta glucan and gliclazide may be considered to reduce oxidative stress in diabetic brain and sciatic nerve and may be used as a protective agent against diabetic damage of brain and sciatic nerve.”

Oxidative Damage/Stress: Sener G, Eksioglu-Demiraop E, Cetiner M, Ercan F, Yegen BC; “beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects.” European J Pharmacology; 542(1-3):170-178; Epub May 2006. Aug 7 2006. Quote: “Methotrexate is an antifolate [antimetabolite chemotherapy drug] that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae [disease condition caused by a disease], where oxidative stress [free radical damage] is noticeable. … Thus, the findings of the present study suggest that beta-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis [white immune cell death], oxidative [free radical] tissue injury and thereby the intestinal and hepatorenal [liver or kidney] side effects of methotrexate treatment.”

Oxidative Damage / Liver Toxicity: Toklu HZ, Sehirili AO, Velioglu-Ogunc A, Centinel S, Sener G; “Acetaminophen-induced toxicity is prevented by beta-d-glucan treatment in mice.” European J Pharmacology; 543(1-3):133-40; Epub 2006 Jun; Jun 2, 2006. Quote: “The protective effect of beta-glucan against oxidative injury caused by acetaminophen [Tylenol, Anacin 3, Tempra, Datril] was studied in mice liver…Acetaminophen caused a significant decrease in the GSH level of the tissue, which was accompanied with significant increases in the hepatic luminol and lucigenin chemiluminescence values, malondialdehyde level, MPO activity and collagen content. Similarly, serum ALT, AST levels, as well as LDH and TNF-alpha, were elevated in the acetaminophen-treated group…beta-d-glucan treatment reversed all of these [liver toxicity] biochemical indices, as well as histopathological alterations that were induced by acetaminophen. In conclusion, these results suggest that beta-d-glucan exerts cytoprotective effects against oxidative injury through its antioxidant properties and may be of therapeutic use in preventing acetaminophen toxicity.”

Oxidative Organ Damage: Toklu HZ, Sener G, “Beta-glucan protects against burn-induced oxidative organ damage in rats,” Int. Immunopharmacol; 6(2):156-69, Marmara U., Istanbul, Turkey; Epub Aug 2005/Feb 2006. Quote:“Thermal injury may lead to systemic inflammatory response, and multiple organ failure. The results indicate that both systemic and local administration of beta-glucan were effective against burn-induced oxidative tissue damage in the rat. Beta-glucan, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, beta-glucans merit consideration as therapeutic agents in the treatment of burn injuries.”

Oxidative Tissue Damage / Liver-Kidney: Sener G, Eksioglu-Demiraop E, Cetiner M, Ercan F, Yegen BC; “beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects.” European J Pharmacology; 542(1-3):170-178; Epub May 2006. Aug 7 2006. Quote: “Methotrexate is an antifolate that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae [disease condition caused by a disease], where oxidative stress is noticeable. … Thus, the findings of the present study suggest that beta-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis [white immune cell death], oxidative tissue injury and thereby the intestinal and hepatorenal [liver or kidney] side effects of methotrexate treatment.”

P

Pancreatitis : Koliakos NN, Renieris G, Sotiropoulos D, et al, “Immunomodulation Through Beta-D-glucan in Chemically-Induced Necrotizing Pancreatitis,” J Surg Res, 261:74-84, PMID: 33421796, https://doi.org/10.1016/j.jss.2020.12.020 , Jan 6, 2021. Quote: “21 -d survival was prolonged after pretreatment or treatment with B-D-glucan; …Bacterial load was lower after pretreatment or treatment with B-D-glucan … . Tumor necrosis factor alpha [TNF alpha] production from stimulated peripheral blood mononuclear cells was significantly decreased, whereas interleukin 10 production remained unaltered after pretreatment or treatment with B-D-glucan. Conclusion: B-D-glucan reduces mortality of experimental pancreatitis in vivo. This is mediated through attenuation of cytokine production and prevention of bacterial translocation.”

Pancreatitis : Browder IW., Williams D., Sherwood E., McNamee R., Jones E., DiLuzio N., “Protective effect of glucan-enhanced macrophage function in experimental pancreatitis, Am J or Surgery,153:25-33, 1987

Paracoccidioidomycosis : Meira, D.A., et al; “The Use of Glucan as Immunostimulant in the Treatment of Paracoccidioidomycosis;” Am J. Trop Med Hyg 55(5), 496-503; Dept of Trop Dis, Dept of Microbio, State U of Sao Paulo, Brazil. 1996. Quote: “…glucan enhances the immune response through stimulation of macrophages by increasing their number, size, and function, stimulates secretion of lysozyme and TNF by activated macrophages, increases the phagocytosis of antigens, activates the formation of granulocyte and monocyte colonies, and factors increased activity of T and B lymphocytes, as well as complement activation.”

Parasites:

Parasites: Trichinosis (Trichinella spiralis):Liu Yi, Liu X, Yang L, et al, “Adjuvanticity of B-Glucan for Vaccine Against Trichinella spiralis,” Front Cell Dev Biol,9:701708, https://doi.org/10.3389/fcell.2021.701708 . PMID: 34322488, Jul 12 2021. Quote: “In this paper, we first observed the adjuvanticity of B-glucan as adjuvant for defensing [parasitic] helminth T. spiralis [Trichinosis – parasite usually from pork] in vivo. …B-glucan as an adjuvant, have the capacity to protect against T. spiralis infection via activating both Th1 and Th2 immune response.”

Parasites: Vetvicka V, Fernandez-Boltran R, “B-Glucan and Parasites,” Helminthologia, 55(3):177-184, PMID: 316626645, Jul 28 2018. Quote: “Immunosuppression caused by parasitic infections represents the foremost way by which the parasites overcome or escape the host’s immune response. …Our review is focused on the possible roll of glucan’s action in antiparasite therapies and vaccine strategies. …glucan studies have consistently shown its ability to offer solid protection against parasitic infections. The overwhelming conclusion reached from this review is that, as an adjuvant, glucan can be as effective as, and at the same time safer than, conventional bacterial or other adjuvants.”

Parasites:” Rondanelli M, Opizzi A, Monteferrario F, “The Biological activity of beta-glucans”; Minerva Medical; 100(3):237-245; Pub Med 19571787; Jun 2009. Quote: “…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. …-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].”

Parasites: Flatworms/Tapeworms:Velebny S, et al, “Impact of treatment with prasiquantel, silymarin [milk thistle] and/or beta-glucan on pathophysiological markers of liver damage and fibrosis in mice infected with Mesocestoides vogae (Cestoda [flat worms including tape worms]) tetrathyridia;” Parasitological Institute, Slavak Republic;J Helminthol, 1-9, PubMed 18394210; April 8, 2008. Quote: “These results showed that combined treatment of PZQ (anthelmintic drug praziquante) with silymarin [milk thistle] and/or beta-glucan was able to ameliorate or suppress fibrogenesis in the liver, protect liver cells from oxidative damage and, possibly stimulate regeneration of the parenchyma.”

Parasites: Jordan F.; “An Effective Immune Response Potentiator– Beta-1,3/1,6-glucan Derived from Yeast Cell Wall,” Macrophage Technologies Publication, pp 1-7; 1998.

Parasites: Williams D.L., Browder I. and DiLuzio N.R., “Soluble phosphorylated glucan: methods and compositions for wound healing,” U.S. Patent 4975421, Issued Dec 4, 1990. Quote: “The soluble phosphorylated glucans are useful for promoting the wound healing process. The soluble phosphorylated glucans are also useful for prophylactic and therapeutic applications against neoplastic, bacteria, viral, fungal and parasitic diseases.”

Parasitic Infection: DiLuzio N.R., ”Immunopharmacology of glucan: a broad spectrum enhancer of host defense mechanisms,” Trends in Pharmacol. SCI., 4:344-347. Dept of Physiology, Tulane U, New Orleans, LA. 1983. Quote: (p347) “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.”

Parasitic Infection: DiLuzio N.R. and Williams D.L., “The Roll of Glucan in the Prevention and Modification of Microparasitic Diseases;” in Chemical Regulation of Immunology in Veterinary Medicine, Alan R. Liss, Inc.; pp. 443-456. 1984.

Parkinson’s Disease: Rahayu M, Kurniawan SN, Anggraini DJ, “The Effect of Beta Glucan of Saccharomyces Cerevisae on the increase of the number of brain cells in substantia nigra Brain of Parkinson’s Wistar Strain Rat (Ratus Norvegicus) Model induced with Rotenone,” Malang Neurology Journal, [S.I.], v. 1, n. 1, p. 17-22, ISSN 2442-5001, Jan 2015. Quote: “Beta glucan from Saccharomyces cerevisae is very potential to be used as a regenerative therapy of Parkinson’s disease. Beta glucan can increase the mobilization of hematopoietic stem cells (HSCs) from the bone marrow into the damaged tissues. …Conclusion: The addition of Saccharomyces cerevisae with a dose of 18mg/kgBB, 36mg/kgBBd and 72mg/kg BB is able to increase the number of brain cells in the subtantia nigra of the brain of Parkinson’s Strain Wistar rat model significantly.”

Particle Size: See also Micronization, Dectin 1 Receptor and Immune Cell Receptors

Particle Size – Beta Glucan – Jialu X, Me Q, et al, “Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth [mouse studies],” Nature Communications, 13110, https://doi.org/10.1035/s41467-021-27750-21 , Jan 10 2022. Quote, “Intriguingly, the induction anti-cancer immunity appears to inversely correlate with the size of nanoparticles. Small size …showed better efficiency in controlling tumor growth after intratumor injection compared with middle and large size of YC NPs.”

Particle Size: Durrell K, Vetvicka V, “Beta-glucan: A space that ‘lacks the prestige’ of traditional nutrients, but holds great potential,” Nutrition Insight, pp1-2, www.nutritioninsight, Sep 04 2019. Quote: “Vetvicka further notes … due to their larger size, beta-glucans are normally not phagocytized by gut cells and, therefore, are blocked from entering the body. [Note: see also micronization]. Note: Many research reports disagree with the Vetvicka conclusion.

Particle Size: Farris E, Brown DM, Ramer-ETait, Pannnier AK, “Miro-and nanoparticulates for DNA vaccine delivery” Exp Biol Med (Maywood) pii:1535370216643771; PMID: 27048557; April 4, 2016. Quote: “In contrast, nanoparticle encapsulation leads to increased internalization, overall greater transfection efficiency, and the ability to increase uptake across mucosal surfaces. Moreover, selection of the appropriate biomaterial can lead to increased immune stimulation and activation through triggering innate immune response receptors and target DNA to professional antigen presenting cells. Finally, the selection of materials with the appropriate properties to achieve efficient delivery through administration routes conducive to high patient compliance and capable of generating systemic and local (i.e. mucosal) immunity can lead to more effective humoral and cellular protective immune responses.” Note: 1 Nano = .001 Microns

Particle Size: Vetvicka V, “Beta Glucan, Natures Secret-3rd Edition,” p 153-154, 2015. Quote: “It is apparent that, in the case of macrophages and phagocytosis, size really does not matter.” Note: V Vetvicka is the only researcher found to date to assert beta glucan particle size does not matter in macrophages activation and phagocytosis – see extensive additional research for support that particle size does matter. Further, V Vetvicka contradicts this statement in the quote above dated Sept 4, 2019 under “Particle Size,” elsewhere which indicates particle size is or could be important.

Particle Size: Pacheco P, et al, “Effects of microparticle size and Fc density on macrophage phagocytosis.” PLoS One;8(4):e60989. PMID:23630577; PMCID:PMC363260 Apr 22 2013. Quote: “The percentage of phagocytic macrophages was found to be strongly dependent on both the particle size and the particle Fc density. …Interaction with the smaller particles (0.5 µm and 1 µm) at a low Fc density resulted in a greater percentage of phagocytic macrophages than with high Fc density. …Therefore, larger microparticles (3 µm and 4.5 µm)may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles (0.5 µm to 2 µm) can deliver bio-active substances to a greater percentage of the macrophage population.” Note: Fc is an antibody molecule known as the crystallizable fragment. µm = microns. Larger Particle sizes in this study were 3 to 4.5 µm (microns) However, particles from 5 to 100+ µm (microns) are considered aggregated or agglomerated and sometimes referred to as globular due to increased size and reduced phagocytic activity.

Particle Size / Micronization / Endocytosis: Keiji H, Hiroshi T, “Endocytosis of Particle Formulations by Macrophages and Its Application to Clinical Treatment,” Chapter 16; 0706 2012. Quote: “Particle size is likely the primary factor that governs endocytic uptake of particles. The optimum size of particles for efficient endocytic uptake varies according to the cell type. Macrophage cells are able to ingest large particles having a diameter between 1 micron and 10 microns to eliminate invaders from outside the body. The optimal sizes of the particles for the uptake by alveolar macrophages [primarily in the lungs] range between 3 microns and 6 microns, but those by peritoneal macrophages and peripheral blood mononuclear cells are reportedly from 0.3 microns to 1.1 microns.” Note: Endocytosis is the process of actively transporting molecules into the cell by engulfing such molecules with the cell membrane. The term “micronized” in reference to beta 1,3/1,6 glucan particles refers to insoluble particles 5 microns or less in size, with uniformity in micronized particles in size in a dose an important variable.

Particle Size: Zechner-Krpan V, Petravic-Tominac V, Galovic P, Galovic V, Filipovic-Grcic J, Srecec S, “Application of Different Drying Methods on B-Glucan Isolated from Spent Brewer’s Yeast Using Alkaline Procedure” University of Zagreb, Agriculturae Conspectus Scientificus, Vol 75, No 1 2010. Quote: “The macrophage phagocytosis is more enhanced by microparticulate B-glucan than by its aggregated form. Biological activity of B-glucan can be improved by reducing the size of its particles. …The particles having 1-2 µm [microns] in diameter are optimally phagocytized by macrophages.”

Particle Size: Champion JA, Walker A, Mitragotri S, “Role of particle size in phagocytosis of polymeric microspheres.” Pharmaceutical research 25: 1815–1821 .PMIC 18373181, PMC 2793372. 2008

Particle Size – Micronization: Spence JK, et al, “Increased dissolution rate and bioavailability through co-micronization with microcrystalline cellulose,” Pharm Dev Technol, 10(4);451-60, PMID 16370174, 2005. Quote: “Micronization is a commonly used enabling technology to improve the bioavailability of compounds where absorption is dissolution rate limited.”

Particle Size – Micronization: Rasenack N, Muller BW, “Micron-size drug particles: common and novel micronization techniques,” Pharm Dev Technol; 9(1):1:14, PMID 1500462; 2004. Quote: “Many drugs, especially newly developed substances, are poorly water soluble, which limits their oral bioavailability. The dissolution rate can be enhanced by using micronized drugs.”

Particle Size: Hunter KW, Gault RA, Berner MD, “Preparation of microparticulate B-glucan from Saccharomyces cerevisiae for use in immune potentiation.” Letters in Applied Microbiology,” Vol 35 Issue 4, 267-271, October 2002. Quote: “…there was evidence that macrophages, key target cells for the immunopharmacological activity of B-glucans, preferentially ingest particles in the 1-2-µ (micron) diameter size range. Compared with the aggregated [5-100-µ micron diameter] form of B-glucan, the B-glucan microparticles remain in suspension longer for pharmaceutical applications and are more effective at enhancing phagocytosis by peritoneal macrophages following oral administration. …Although both aggregated and microparticulate glucans enhanced peritoneal macrophage activation when administered orally in mice, the microparticulate glucan was significantly better than the aggregated form.”

Particle Size: Jordan F, Hunter Jr. KW, Gault R, “Method for preparing small particle size glucan in a dry material,” U.S. Patent 6,476,003. November 2002. Quote: “The greater generation and/or production of NO (Nitric Oxide) demonstrates the enhanced activity of the macrophage with a small particle size glucan which is indicative of an activity level of an immune system. … The measurement of NO production is indicative of an oxidative burst that kills and/or destroys the ingested microbes and/or particles by the macrophage. …As a glucan re-aggregates into particles of greater than one micron in diameter, it appears to pass through an animal or human digestive system without substantially complete absorption. … As the glucan re-aggregates to a size of greater than one micron in diameter, some of the beneficial effect of the glucan is not achieved because the macrophage receptors are not activated as readily by glucan greater than one micron in diameter because the receptor size on corresponding cells and molecules that accept the glucan is generally about one micron in size. …The greater percentage phagocytosis demonstrates the enhanced activity of the macrophage and the small particle size glucan’s ability to activate the immune system.”

Particle Size: , Hunter Jr. KW, Gault R, Jordan F, “Mode of Action of B-Glucan Immunopotentiators,” Department of Microbiology, University of Nevada School of Medicine, Oct 1998.

Globular Glucan (μg/ml)

Sonicated Microparticulate Glucan (μg/ml)

Media

Nitric Oxide (μM)

275

600

Quote: “…these data do indicate Glucan particle size is an important factor in the production of nitric oxide. Nitric oxide is generated during the “oxidative burst” that kills ingested microbes [bacteria, viruses, fungi, parasites, etc]. This would suggest that the small particle glucan has greater ability to enhance the immune system than the globular form of glucan.”

Particle Size – Smaller more Effective: Donzis B. A.; Substantially purified beta (1,3) finely ground yeast cell wall glucan composition with dermatological and nutritional uses; U.S. Patent 5702719; 1997. Quote: “The preferred particle size of the find grind glucan product is about 1.0 micron or less and more preferably, .20 microns or less.” [2,000 nanometers or less]

Particle Size – Smaller more Effective: Donzis B. A.; Substantially purified beta (1,3) finely ground yeast cell wall glucan composition with dermatological and nutritional uses; U.S. Patent 5576015; 1996. Quote: “Upon oral administration, the smaller or finer particle sized glucan is more quickly dissolved in the gastrointestinal tract and consequently, more readily absorbed.”

Particle Size: Tabata Y, Ikada Y, “Effect of the Size and Surface-Charge of Polymer Microspheres on Their Phagocytosis by Macrophage.” Biomaterials 9: 356–362.1988 . PMID 3214660. Quote: “It was found that the maximal phagocytosis of polystyrene and phenylated polyacrolein microspheres took place when their size was in the range 1.0-2.0 microns.”

Pathogens / Colds-Human Clinical Trial : Aulinger A, Riede L, Bothe G, Busch R, Gruenwald J, “Yeast (1,3)-(1-6)-beta-glucan helps to maintain the body’s defense against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects [162]. ” Eur J Nutr, 52: 1913-1918; Jan 23, 2013. Quote: “…supplementation with insoluble yeast (1,3)-(1-6)-beta-glucan reduced the number of symptomatic common cold infections by 25% as compared to placebo. …Beta-glucan significantly reduced sleep difficulties caused by cold episode…the yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.”

Pediatrics/Children-Human Clinical Trial-Respiratory Infections: Li F, Jin X, Liu B, Zhuang W, Scalabrin D, “Follow-up Formula Consumption [FUF] in 3- to 4-Year-Olds and [Acute] Respiratory Infections [ARI]: an RCT.” , Pediatrics. 133(6):e1533-40. Jun 2014. Quote: “…Our objective was to determine if a follow-up formula (FUF) containing DHA,…prebiotics.. and yeast B-glucan affects incidence of respiratory infections … in healthy children.” The study was, “…a double-blind, randomized, controlled, prospective trial, 3-4 year old children. …Daily consumption of a FUF was associated with fewer episodes and shorter duration of ARI [ acute respiratory infections], as well as less antibiotic use.”

Periapical Bone Resorption :Stashenko, et al., “Reduction of Infection-Stimulated Periapical Bone Resorption by the Biological Response Modifier PGG Glucan”, J. Dent. Res.; 74(1):323-330; 1995.* Dept of Cytokine Biology, Forsyth Dental Ctr, Boston, MA. Quote: “PGG glucan-treated animals had significantly less infection-stimulated periapical bone resorption than control animals…”

Periodontal Disease

Periodontal Disease-Diabetes: Assi DV, Pereira ANJ, et al, “Dose-response effect of prebiotic ingestion (B-glucans isolated from Saccharomyces cerevisiae in diabetic rats with periodontal disease,” Diabetol Metab Syndr, 13(1);111., PMID: 34663444, https://doi.org/10.1186/s13098-021-00729-1 , Oct 18 2021. Quote: Periodontal disease is one of the most frequent comorbidities in diabetic patients and can contribute to poor blood glucose control. …BG [Bea-glucans] ingestion reduced ABL [alveolar bone loss] and improved inflammatory profile in a dose-dependent manner.”

Periodontal Disease: Da Silva GC, Costa ED, et al, “Experimental periodontal disease triggers coronary endothelial dysfunction in middle-aged rats: preventive effect of a prebiotic B-glucan,” J Gerontol A Bil Sci Med Sci, glab066, PMID: 33677586, https://doi.org/10.1093/gerona/glab066, Mar 3, 2021. Quote: “Treatment with B-glucan effectively reduced bone loss in periodontal disease and delayed endothelial dysfunction in the coronary artery. …These results suggest that B-glucan has a beneficial effect on the coronary vascular bed.”

Periodontal Disease – Diabetes: Silva VO, Lobato RV, et al, “Effects of B-Glucans Ingestion on Alveolar Bone Loss, Intestinal Morphology, Systemic Inflammatory Profile, and Pancreatic B-Cell Function in Rats with Periodontitis and Diabetes,” Nutrients, 14;9(9). PMID 28906456, Sept 14, 2017, Quote: “The study aimed to evaluate the effects of B-glucan ingestion (Saccharomyces cerevisiae) on the plasmatic levels of tumor necrosis factor-a (TNF-a0 and interleukin-10 (IL-10), alveolar bone loss, and pancreatic B-cell function (HOMA_BF) in diabetic rats with periodontal disease (PD). …B-glucan ingestion reduced the systemic inflammatory profile, prevented alveolar bone loss, and improved B-cell function in diabetic animals.”

Periodontal Disease – Diabetes: Silva VO, Lobato RV, et al, “B-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease,” PLoS One, Aug 20;10(8):e0134742. PMID 26291983: PMC4546386, 2015. Quote: “…oral ingestion of β-glucans isolated from Saccharomyces cereviseae … reduced the amount of alveolar bone loss in animals with periodontal [gum] disease in both the diabetic and non-diabetic groups). β-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease. It was concluded that treatment with β-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease.”

Peritonitis: Lahnborg G., Hedstrom K.G., Nord C.E.; “The Effect of Glucan – A Host Resistance Activator and Ampicillin on Experimental Intraabdominal Sepsis”. Journal of Reticuloendothelial Society. 32: 347-353. 1982.* Quote: “It is concluded that glucan, in combination with ampicillin, has a significant effect on the survival rate of rats with induced peritonitis, probably by enhancing the activities of the reticuloendothelial system, an important part of the total host resistance.”

Peritonitis: 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.. Dept of Pathology, Channing Lab, Brigham and Women’s Hospital, Boston, MA 1992.* Quote: “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.”

Phagocytic Receptors-Human Study: Czop J.K., Kay J., Isolation and Characterization of B-glucan Receptors on Human Mononuclear Phagocytes. J. Exp. Medicine; V.173:1511-1520. Dept of Med, Harvard Med Sch, Boston, MA. 1991. Quote: “…human alveolar macrophages …possess phagocytic receptors of comparable ligand specificity for the Beta glucans commonly present in yeasts and fungi.”*

Phagocytosis:

Phagocytosis: Zhang Y, Liu X, Zhao J, et al, “The phagocytic receptors of B-glucan,” Int J or Biological Macromolecules, Vol 205, pp40-441, PMID: 35202631, https://doi.org/10.1016/j.ifbiomac.2022.02.111 , Feb 23 2022. Quote: “Phagocytosis is a cellular process maintaining tissue balance and plays an essential role in initiating the innate immune response. These receptors …also bridge the gap between extracellular and intracellular communication, leading to signal transduction and production of inflammatory mediators, which are crucial for clearing the invading pathogens and maintaining cell homeostasis. ..B-glucan…By binding to specific receptors on immune cells and activating intracellular signal transduction pathways, causes phagocytosis and promotes the release of cytokines.”

Phagocytosis: – Respiratory Burst (ROS): Dutta O, Espinosa V, et al, “Dectin-1 Promotes Type I and III Interferon Expression to Support Optimal Antifungal Immunity in the Lung,” Front Cell Infect Microbiol, 10:321, https://doi.org/10.3389/fcimb.2020.00321, PMID: 32733815, Jul 8 2020. Quote: “The downstream outcomes of B-glucan recognition by dectin-1 include the production of various cytokines, including TNF-a, IL6, and IL-22, generation of reactive oxygen species (ROS), as well as expression of neutrophil chemoattractiants, MIP-1a and MIP-2. Phagocytosis of a microbe such as fungal conidia initiates a process known as a respiratory burst. Oxygen consumption by the phagocyte increases and the enzyme NADPH oxidase relocates to the phagosome and produces ROS to help contain and eliminate the invading threat. ROS [reactive oxygen species] can directly kill microbes by causing oxidative damage to their DNA, cell membrane and wall components. …In aggregate, these finding indicate ROS [reactive oxygen species] are essential regulators of the host response to fungal infection both as direct effectors of fungal cell inactivation and regulators of inflammation.”

Phagocytosis: Camili , Eren E, Williams DL, et al, “Impaired phagocytosis directs human monocyte activation in response to fungal derived B-glucan particles,” Eur J Immunol, 48(5):757-770, PMID 29313961. May 2018. Quote, “Recognition of the fungal cell wall carbohydrate B-glucan by the host receptor Dectin-1 elicits broad immunomodulatory responses, such as phagocytosis and activation of oxidative burst. These responses are essential for engulfing and killing fungal pathogens.”

Phagocytosis: Vetvicka, V, “Beta Glucan, Natures Secret” , 3rd Edition, Self Published, pp153-154, 2015. Quote: “…macrophages have glucan receptors the size of only several molecules. Yet they are able to phagocytose material of more than 20% of their own size. It is apparent that, in the case of macrophages and phagocytosis, size really does not matter…” [Note: V Vetvicka’ position that beta glucan particle size does not matter in phagocytosis is the position found for only Vetvicka based on extensive beta glucan’ phagocytosis research reviewed with several presented below. Macrophages are generally 10-12 microns in diameter, indicating V Vetvicka appears to assume macrophage ability to phagocytize materials of 20% more or 12-15 microns in size.]

Phagocytosis: Pacheco P, et al, “Effects of microparticle size and Fc density on macrophage phagocytosis.” PLoS One;8(4):e60989. PMID:23630577; PMCID:PMC363260 Apr 22 2013 . Quote: “The percentage of phagocytic macrophages was found to be strongly dependent on both the particle size and the particle Fc density. …Interaction with the smaller particles (0.5 µm and 1 µm) at a low Fc density resulted in a greater percentage of phagocytic macrophages than with high Fc density. …Therefore, larger microparticles (3 µm and 4.5 µm)may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles (0.5 µm to 2 µm) can deliver bio-active substances to a greater percentage of the macrophage population.” Note: Fc is an antibody molecule known as the crystallizable fragment. µm = microns. Larger Particle sizes in this study were 3 to 4.5 µm (microns) However, particles from 5 to 100+ µm (microns) are considered aggregated or agglomerated and sometimes referred to as globular due to increased size and reduced phagocytic activity.

Phagocytosis: Zechner-Krpan V, Petravic-Tominac V, Galovic P, Galovic V, Filipovic-Grcic J, Srecec S, “Application of Different Drying Methods on B-Glucan Isolated from Spent Brewer’s Yeast Using Alkaline Procedure,” University of Zagreb, Agriculturae Conspectus Scientificus, Vol 75, No 1 2010. Quote: “The macrophage phagocytosis is more enhanced by microparticulate B-glucan than by its aggregated form. Biological activity of B-glucan can be improved by reducing the size of its particles. …The particles having 1-2 µm [microns]in diameter are optimally phagocytized by macrophages.”

Phagocytosis: Champion JA, Walker A, Mitragotri S, “Role of particle size in phagocytosis of polymeric microspheres.” Pharmaceutical research 25: 1815–1821 PMIC 18373181, PMC 2793372.2008, 2008. Quote: “Particles possessing diameters of 2-3 microm exhibited maximal phagocytosis and attachment….”

Phagocytosis: Freitas Jr, RA, “15.4.3.1 Phagocytes, Phagocytosis, and the RES – Macrophages;” Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX 2003. Quote: “The presence and activity of phagocytes is particularly related to the presence of small particles. …Maximum stimulus occurs at average particle sizes in the 0.1-2.0 [micron] range… Human blood monocytes [macrophage precursors] readily ingest inert 0.39 micron particles, rarely ingest 1.52 micron particles, and never ingest 5.1 micron particles.”

Phagocytosis:: Hunter KW, Gault RA, Berner MD, “Preparation of microparticulate B-glucan from Saccharomyces cerevisiae for use in immune potentiation.” Letters in Applied Microbiology,” Vol 35 Issue 4, 267-271, PubMed 123586685, October 2002. Quote: “…there was evidence that macrophages, key target cells for the immunopharmacological activity of B-glucans, preferentially ingest particles in the 1-2-µ (micron) diameter size range. …This microparticulate beta-glucan …following oral administration at 0.1 mg kg(-1) for 14 d, enhanced phagocytosis of mouse peritoneal macrophages significantly better than did aggregated beta-glucan particles.”

Phagocytosis: Jordan F, Hunter Jr. KW, Gault R, “Method for preparing small particle size glucan in a dry material,” U.S. Patent 6,476,003. November 2002. Quote: “…The greater percentage phagocytosis demonstrates the enhanced activity of the macrophage and the small particle size glucan’s ability to activate the immune system.”

Phagocytosis: Brandwood A, et al, “Phagocytosis of carbon particles by macrophages in vitro.” Biomaterials, 13(9):646-8, . PMID 1391413 1992. Quote: “Particles up to 20 microns diameter were phagocytosed. Larger particles were not phagocytosed.”

Phagocytosis: Tabata Y, Ikada Y, “Effect of the Size and Surface-Charge of Polymer Microspheres on Their Phagocytosis by Macrophage.” Biomaterials 9: 356–362.. PMID 3214660 1988. Quote: “It was found that the maximal phagocytosis of polystyrene and phenylated polyacrolein microspheres took place when their size was in the range 1.0-2.0 microns.”

Pink Eye-Conjunctivitis : Lee HS, Kwon JY, Joo CK. “Topical Administration of B-1,3-Glucan to Modulate Allergic Conjunctivitis in a Murine Model.” Invest Ophthalmol Vis Sci,, 57(3), 1352-60; PMID 27002295; Mar 2016.” Quote: “BG is capable of stimulating IL-10-producing CD4 [Helper T cells]+ T cells and suppressing both the Th2 response in draining LNs and conjunctival eosinophil infiltration. We therefore demonstrated the therapeutic potential of topical BG administration for allergic conjunctivitis.“ Note: LN refers to Lymph Nodes and BG to Beta Glucan.

Platelets: Saluk-Juszczak J, Krolewska K, Wachowicz B. “Response of blood platelets to beta-glucan from Saccharomyces cerevisiae.” Platelets, 21(1):37-43. doi: 10.3109/09537100903359306; PMID: 1989-1527; 2010. Quote: “The obtained results indicate that beta-glucan has the inhibitory effects on platelet aggregation and secretion. … and therefore may be beneficial in the prevention of the excessive blood platelet activation-related diseases, such as cardiovascular or inflammatory diseases.”

Platelet Production: Jamas S., Easson D., Ostroff G.R.; “Use of aqueous soluble glucan preparations to stimulate platelet production.” U.S. Patent 5532223. Issued July 2, 1996.*

Platelet Production: Jamas S., Easson D., Ostroff G.R.; “Use of neutral soluble glucan preparations to stimulate platelet production.” U.S. Patent 5488040. Issued January 30, 1996.*

Platelet Production: Spiros J.; Use of neutral soluble glucan preparations to stimulate platelet production; U.S. Patent 5488040; 1996.

Platelet Recovery: Pachen ML, MacVittie TJ, “Comparative effects of soluble and particulate glucans on survival in irradiated mice,” J Biol Response Mod 5(1):45-60. Experimental Hematology Dept, Armed Forces Radiobiology Research Inst, Bethesda, MD. Feb 1986.

Pneumonia: See also “Upper Respiratory Infection”

Pneumonia – Bacterial Infections: Masterson CH, Murphy EJ, et al, “Purified B-glucans from the Shiitake mushroom ameliorates antibiotic-resistant Klebsiella pneumoniae-induced pulmonary sepsis,” Lett Appl Microbiol, PMID: 32706908, DOI: 10.1111/lam.12258, Jul 24 2020. Quote: “Bacterial infection remains the main cause of Acute Respiratory Distress Syndrome (ARDS) and is a leading cause of death and disability in critically ill patients. Here we report on the use of purified B-glucan (Lentinan) extracts …that can reduce infection by a multidrug-resistant clinical isolate of K. Pneumonniae in a rodent pneumonia model, likely through immunomodulation. …In conclusion administration of Lentinan [B-glucan] to treat sepsis-induced lung injury appears safe and effective and may exert its effects in an immunomodulatory manner.” [Ameliorate: to make better, improve. Lentinan is a B-1,3 beta glucan with B-1-6 branching and a molecular weight of 500,000 Da.]

Pneumonia: Akramlene D, Konddrotas A, et al, “Effects of B-glucans on the immune system,” Medicina (Kaunas), 43(8), Kaunas U of Med, Lithuania, Aug 6 2007. Quote: “It has been common knowledge in the scientific community that B-glucan is the most known powerful immune stimulant and a very powerful antagonist to both benign and malignant tumors; it lowers cholesterol and triglyceride level, normalizes blood sugar level, heals and rejuvenates the skin and has various other benefits. …B-Glucan itself can elicit broad anti-infective effects. Staphylococcus aureus, Escherichia coli, Candida albicans, Pneumocystis carinii, Listeria monocytogenes, Leishmania donovani, Influenza virus are microorganisms, against which a protective effect of B-glucan has been established.”

Pneumonia: Steele C, Marrero L, Brown GD, et al, “Alveolar macrophage-mediaenhanced the recovery of peripheral blood white cell numbers, platelet numbers, and hematocrit values. In addition, both agents increased endogenous pluripotent hemopoietic stem cell numbers in sublethally irradiated mice. … killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor.” Department of Pediatrics, Division of Pulmonology, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. J Exp Med. 198(11): 1677-88; Dec 2003. Quote: “…these results show that nonopsonic phagocytosis and subsequent killing of P. carinii [a frequent cause of pneumonia in immunocompromised individuals] by alveolar macrophages is dependent upon recognition by the Dectin-1 beta-glucan receptor [activated by beta-glucan ingestion in the Dectin-1 beta-glucan receptor].”

Pneumonia-Human Study: Maurici da Rocha e Silva et al; “Infection Prevention in Patients with Severe Multiple Trauma with the Immunomodulator Beta 1-3 Polyglucose (glucan);” Surgery, Gynecology & Obstetrics; 177:383-388. 1993. Quote: “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 instances 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.”

Pneumocystis: Cushion MT, Walzer PD, “Preclinical drug discovery for new anti-pneumocystis compounds,” Curr Med Chem 16(20):2514-2530, WMD, 2009. Note: Pneumocystis pneumonia (PCP) is a serious infection causing inflammation and fluid buildup in the lungs that is caused by a fungus, Pneumocystis Jirovecii, that spreads through the air.

Post Operative Infections:

Post Operative Infections-Human Study:: Browder IW. Williams DL, Di Luzio NR, et al, “Modification of postoperative C-albicans sepsis by glucan immunostimulation.” Int J Immunopharmacol, PubMed 6724765 , 6:19-26, 1984. Quote: “…glucan increased survival and reduced renal pathology associated with C. albicans challenge in the post operative period. These observations suggest that Biologic Response Modifiers such as glucan may be effectively employed in patients who are at risk for post operative infections.”

Prebiotic

Prebiotic – Periodontal Disease Da Silva GC, Costa ED, et al, “Experimental periodontal disease triggers coronary endothelial dysfunction in middle-aged rats: preventive effect of a prebiotic B-glucan,” J Gerontol A Bil Sci Med Sci, glab066, PMID: 33677586, https://doi.org/10.1093/gerona/glab066, Mar 3, 2021. Quote: “Treatment with B-glucan effectively reduced bone loss in periodontal disease and delayed endothelial dysfunction in the coronary artery. …These results suggest that B-glucan has a beneficial effect on the coronary vascular bed.”

Prebiotic – anti-Obesity: Cordero JG, Ruiz BS, et al, “Effectiveness of hydroxycinamates and beta-glucans as dietary tools against obesity and its associated dysfunctions, and their application as nutraceuticals,” Nutr Hosp, Vol 37, Num 5, pp 887-1092, PMID: 32960625, DOI: 10.20960/nh.031125, Sep 22 2020. Quote: Obesity has been related to disorders such as type-2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, among others, which has made of obesity the second cause of preventable death, only behind smoking. Among bioactive compounds, this study will focus on B-glucans, … and hydroxycinnamic acids, …compounds show complex and multifactorial effects, acting as hypolipemic, hypoglycemic, antioxidant, prebiotic and satiating agents. They act by modulating different metabolic pathways, affecting the absorption and metabolism of lipids and carbohydrates, reducing oxidative damage, promoting the proliferation of beneficial bacterial species, and reducing dietary intake.. It may be concluded that …beta-glucans …have potential as a nutritional tool for management of obesity and associated metabolic dysfunctions.” Note: Research in Spanish

Prebiotic – anti-obesity: Muthuramalingam K, Singh V, et al, “Dietary intervention using (1,3)/(1,6)-B-glucan, a fungus-derived soluble prebiotic ameliorates high-fat diet-induced metabolic distress and alters beneficially the gut microbiota in mice model,” Eur J Nutr, doi: 10.1007/s0394-019-021, Pubmed: 31664519, Oct 29 2019. Quote: “B-glucan consumption exhibited anti-obesity property in mice groups fed with HFD [High Fat Diet]. In addition, B-glucan ameliorated HFD-induced hepatic stress, colonic motility and intestinal atrophy (reduction in colon length, goblet cells, and mucosal layer thickness). Further, B-glucan incorporation shifted bacterial community by increasing butyrate-producing bacteria such as Anaerostipes, Coprobacillus, and Roseburia and decreasing reportedly obesiy-associated bacteria such as Parabacteroides and Lactococcus.”

Prebiotic-Beta Glucan: Ciecierska A, Drywien ME, et al, “Nutraceutical functions of beta-glucans in human nutrition,” Rocz Panstw Zakl Hig, [Translation: Roczniki Panstwowego Zakladu Higieny, Responsiveness to the hospital patient needs in Poland], 70(4):315-324, (ISSN: 0035-7715), 2019. Quote: “Beta-glucan[s]…are attributed a number of beneficial health properties, including the prevention and treatment of certain digestive diseases and supporting the immune system. …Beta-glucan reduces cholesterol and glucose concentrations in the blood, which reduces the risk of cardiovascular disease and diabetes. …beta-glucan also exhibits antioxidant properties by scavenging reactive oxygen species, thereby reducing the risk of diseases, including atherosclerosis, cardiovascular diseases, neurodegenerative diseases, diabetes, and cancer. Immunostimulatory and antitumor effects have also been reported. …Beta-glucan belongs to the group of prebiotics which stimulate the growth and activity of the desired natural intestinal microbiota, while inhibiting the growth of pathogens. …Such a number of health benefits resulting from the properties of beta-glucan may play a key role in improving health benefits resulting from the properties of beta-glucan and preventing chronic non-communicable diseases, such as diabetes, hypercholesterolemia, obesity, cardiovascular diseases, and cancer.

Prebiotic Effect-Beta Glucan-Human Study: “Beta-Glucans Improve Growth, Viability and Colonization of Probiotic Microorganisms,” Int J MOl Sci, 13(5): 6026-6039; PMCID:PMC33822753; 2012: Crit Rev Microbiol, PMID 27561003; Aug 25:1-20; 2016. Quote: “Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. …Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. … This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.”

Pressure Ulcers: See Decubitus Ulcers, Ulcers and Wound Healing also

Probiotics -Synbiotics: Vuong V, Muthruamalingam K, et al, “Effects of B-glucan, probiotics, and synbiotics on obesity-associated colitis and hepatic manifestations in C57BL/6J mice,” Eur J Nutr, PMID: 34561722, https://doi.org/10.1007/s00394-021-02668-z , Sep 24, 2021. Quote: “Probiotics and prebiotics are commonly used to improve the gut microbiota. SYN [synbiotics] treatment groups, however, supported the growth of both indigenous and supplemented bacteria while maintaining bacterial diversity. Since prebiotics can support the growth of probiotics, co-administration of these is called synbiotics [SYN]. Obesity-associated colitis can be improved by modulating gut bacteria with B-glucan and probiotics. “

Probiotic Survival-Beta Glucan, Shah A, Gani A, Ahmad M, et al, “B-Glucan as an encapsulating agent: Effect on probiotic survival in simulated gastrointestinal tract.” Int J Biol Macromoi, 82:217-22. PMID 26562556, Fan 2016. Quote: “Three strains of probiotics Lactobacillus casei, Lactobacillus brevis and Lactobacillus plantarum were encapsulated in B-glucan matrix using emulsion technique. Results revealed significant (p<0.05) improvement to tolerance when the encapsulated cells were subjected to stresses like low pH, heat treatment, simulated intestinal conditions and storage.”

Protozoan Infections: 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. Quote: “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.”

Pulmonary: Kimura A, Sherwood R, Goldstein E; “Glucan alteration of pulmonary antibacterial defense.” J Reticuloendothel. Soc. 24:1-11. 1983.

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The Beta Glucan Research Organization is not a commercial marketing entity and has no products of any kind. References and quotes contained herein are for information, education and research purposes only and should not be construed as express or implied representations, endorsements or warranties of The Beta Glucan Research Organization.

Note on various Glucan forms: No commercial brand names of products are presented or endorsed on this research website. Beta 1,3/1,6-D glucan is a baker’s yeast-Saccharomyces cerevisiae, derived beta glucan isolate with a Beta 1,6 linkage (4-8%) and the molecule skewed to the right. MG Glucan is a microparticulate Beta 1,3/1,6 glucan that is primarily uniform homogeneous and non-aggregated Beta 1,3-D glucan that does not significantly reaggregate after the digestive process. “PGG-glucan” is poly-[1,6]-B-D-glucopyranosyl-[1-3]-B-D-glucopyranose (b-1,6/1,3-glucan). Intravesical bacillus Calmette-Guerin is abbreviated as BCG.

“Beta glucans” refers generally, but not always, to Beta- 1,3/1,6-glucan. “Scleroglucan” and “PSAT” are two Beta-1,3/1,6-polysaccharides. Beta glucans are derived primarily from yeast cell wall, various fungi, grains, and mushrooms. Beta 1,4 glucan is derived from oats and barley while not included in this research summary of forms of Beta 1,3/1,6 glucan. Many beta glucans are marketed under various trademark names that are not unique ingredient formulations. Letters such as NSC, WGP and others are associated with brand names and are not specific forms of Beta glucan, although the individual products often contain Beta glucan.

The beta 1,3/1,6 glucan used in various research presented is from multiple sources in various amounts; none determined nor controlled by this website. Check the full research to see sources and amounts used in a specific study. PubMed IDs (PMID) and/or digital object identifiers (DOI) are presented for most research to be able to find additional information on the internet. Human studies and Clinical trials are indexed in Bold Print. No commercial products are presented herein and no claims are made by this non-commercial website regarding any commercial products containing beta 1,3/1,6 glucan or endorsement of the research by various entities herein