History of Beta-1,3/1,6-Glucan Research

 

In the Beginning…

Since the 1940s, scientists and researchers, through Beta Glucan Research, have been evolving the scientific evidence of the remarkable abilities of beta 1,3/1,6 glucan, a long-chained polysaccharide isolated from Saccharomyces cerevisiae cell walls. Sourced primarily from baker’s yeast form of Saccharomyces cerevisiae, beta 1,3/1,6 glucan (B-glucan hereafter) taken orally effectively internalized normalized, potentiated and activated primary immune components of the immune response.

B-glucan as a food is recognized by the FDA as safe with a GRAS classification. Beta 1,3/1,6 glucan taken orally is ingested and internalized by immune cells that in turn recognize potential and actual pathogens. Then, when appropriate, beta glucan activates the immune cascade against pathogens seeking to harm our bodies (self) to avoid negative health issues, including death.  After recognition of non-self pathogens, the immune cells activated by beta glucan then respond to protect against invasion and the immune cells seek to resolve a threat by killing and removing pathogenic invaders in the body’s war.

The story of beta glucan begins with the study of Zymosan, a drug used throughout Europe. Zymosan, an immune stimulator, is composed of a crude mixture of yeast cell wall materials including proteins, lipids, and polysaccharides synthesized into a drug, which unfortunately has many negative side effects in patients.

Louis Pillemer, Ph.D., and his colleagues first studied the drug Zymosan in the 1940s and discovered Zymosan was able to nonspecifically potentiate and modulate the immune system. Zymosan activated the immune response regardless of the type of invader or pathogen, including viruses, bacteria, fungi, parasite and tumors.

The Nicholas DiLuzio PhD Breakthrough

In the 1960s, Nicholas DiLuzio, Ph.D., conducted additional research at Tulane University discovering the active immune-activating compound within the drug component of Zymosan was Beta-1, 3-D-glucan, a long-chained polysaccharide absent the negatives of Zymosan, with to date no known toxicity or side effects. Since that critical break through by Dr. DiLuzio, scientists have determined how beta glucan works to activate the macrophage immune cells and in turn the entire immune response. D.L. Williams PhD and I.W. Browder PhD worked with DiLuzio in much of this research and contributed immensely in the growing body of Beta glucan research.

Beta-1,3-glucan’s beneficial role in treating cancer was illuminated in 1975 by Peter W. Mansell, M.D., and colleagues, as reported in the Journal of the National Cancer Institute. Nodules of malignant skin cancer in nine patients were injected with beta-1,3-glucan. The size of the cancer lesions was “strikingly reduced in as short a period as five days” and in small lesions “resolution was complete,” Dr. Mansell reported.

Harvard and Joyce Czop PhD Make Discovery of the Receptor Site

Research at Harvard University in the 1980s by Joyce Czop, Ph.D., found specific receptor sites for beta glucan that matches a site on the surface of the macrophage. The research of Czop determined the receptor site on the macrophage is a protein complex present in the entire life cycle of the macrophage, even at the point of creation in the bone marrow.

The Harvard University research demonstrated the macrophage, an immune system large white blood cell that “eats” or subjects non-self foreign microbes to phagocytosis, has a specific receptor for beta-1,3-glucan approximately one to 2 microns in size. The Beta glucan acts as a nutritional key that, when internalized in the receptor site, turns on, or activates the macrophage.

The macrophage immune cell then initiates the many functions of this lymphocyte, “big eater,” that devours antigens, pathogens and cellular debris, in addition to communicating with the T-cells in the essential co-stimulatory confirmation of pathogen presence.  Pathogen antigens are then presented by apc cells that after recognition of a pathogen, can be attacked in an appropriate immune response including antibodies, killer cells and cytotoxic cells.

The macrophages subsequently also stimulates bone marrow production of immune supporting substances, the IL-1 cytokine which promotes insulin production and blood platelets. In summary, when the macrophage is activated by receptor contact with a beta glucan particulate, a cascade of events transforms the cells into “an arsenal of defense,” according to Joyce Czop. M.J. Janusz PhD was also prominent in the successful beta glucan research of this period.

Dr. Patchen, Radiation Protection and Anti-Oxidant

In the mid-1980s, researchers at Tulane University School of Medicine reported that beta-1,3-glucan injected directly into chest-wall of malignant ulcers (in women who had already undergone mastectomy and radiation therapy for breast cancer) healed the sores completely. Beta-1,3-glucan’s radiation protection effects were shown in 1985 when the U.S. Armed Forces Radiobiology Research Institute announced the results of their recent experiments. Myra D. Patchen, M.D., and her team at the Institute exposed mice to lethal doses of radiation.

When the mice were given an oral dose of beta-1,3-glucan after the radiation exposure, 70% were completely protected from the damaging effects. Myra Patchen also suggested that beta-1,3-glucan should be considered as an effective way of rebuilding the immune system and preventing infection following chemotherapy and radiation in cancer treatment. Patchen further reported beta-1,3-glucan appears to work as a free-radical scavenger (anti-oxidant) and may even protect the macrophages from damage by radiation, toxins, heavy metals and free-radicals.

Antibiotic Adjuvant and Infection Fighter

Evidence from animal studies demonstrates that beta-1,3-glucan can reduce the amount of conventional antibiotics required in infectious conditions such as peritonitis (inflammation of the membrane lining of the abdominal and pelvic cavities). In mice infected with a bacteria to produce peritonitis, a combination of beta-1,3-glucan and a standard antibiotic increased the long-term survival by 56%.

Bacterial counts were noticeably down within eight hours of the injection and the numbers of key immune cells were markedly higher. “Clinical use of immunomodulators may alter conventional use and dosage of antibiotics,” study director William Browder, M.D., of Tulane University in New Orleans, suggested in 1987.

Dr. Browder also reported on the benefits of using beta-1,3-glucan to stimulate immune response and prevent infection in patients undergoing surgery for physical trauma. In his study, 21 patients received beta-1,3-glucan intravenously every day for one week.

Dr. Browder reported that the incidence of infection in these patients was “significantly reduced” (only a 9.5% incidence of infection) compared to the rate among those who did not receive glucan therapy (49%). The glucan-treated patients also had a greater increase in key immune factors within three days and a much lower mortality rate (0% compared to 29%) than the non-glucan-treated group.

Oral Administration Effective – First Nutritional Supplement Evolves

Although most early research was conducted via test tube (in vitro) or intravenously (IV), in 1989, Phil Wyde PhD at the Baylor College of Medicine, confirmed the effectiveness of a purified particulate beta glucan taken orally was equal or better in potentiating the macrophage immune cells when compared to soluble glucan administered by IV and that small milligram dosages of particulate glucan were effective. The Baylor College of Medicine research was important as it established the oral effectiveness of beta glucan in potentiating the immune response and helped determine a very small dosage in milligrams was an adequate dose for the purified material.

Confirmation of yeast derived glucan’ immune potentiation capabilities taken orally is significant because, as purified Baker’s yeast, this beta glucan could be made available to the public as a nutritional dietary supplement at a cost-effective price and an ease in delivery by mouth versus IV. The Baylor College of Medicine research led to the development of the first nutritional dietary supplement (NSC-24) containing beta glucan, initially in 1995 distributed by ImmuDyne, Inc. for Nutritional Supply Corporation (NSC) and since 1996 manufactured and distributed by Nutritional Scientific Corporation. Today multiple entities are involved in production and distribution of beta glucan.

Donald Carrow MD’ Clinicals – Radiation Protection and More

Donald Carrow, M.D., who performed clinical tests with his patients taking radiation treatment for breast cancer with Beta- 1,3-D-glucan in a nutritional supplement, further notes that the specificity of this macrophage receptor site may explain why beta-1,3-glucan “is one of the most potent stimulators of the immune response.”  Carrow has tested beta-1,3-glucan on a variety of conditions in his clinical practice, including cancer and ulcers, and for general health maintenance.

Carrow injected a skin cancer lesion with 10 mg of beta-1,3-glucan and within three months the tumor had completely disappeared, he reported. Five breast cancer patients undergoing radiation took 7.5 mg daily of beta-1,3-glucan and were free of radiation injuries to the skin. By applying beta-1,3-glucan topically to ulcers on two patients, Carrow reported complete healing them completely within two months. Dr. Carrow says that “there is now evidence to show that beta-1,3-glucan is, from an evolutionary point of view, the most widely and most commonly observed macrophage activator in nature.” Note: Dr. Carrow is now deceased.

Fungal Clinicals a Plus for Beta Glucan

Beta-1,3-glucan’s capabilities in nutritionally potentiating the immune response in resisting and conquering infections is extensively documented. Scientists at the State University of São Paulo in Brazil tested beta-1,3-glucan’s ability to potentiate the immune system against a fungal skin infection. Nine patients with serious fungal infections were given beta-1,3-glucan intravenously once weekly for one month, followed by monthly doses for 11 months. The patients also received a conventional antifungal drug.

There was only one case of relapse among these patients, while another group of eight infected patients who were treated only with the antifungal drug had five relapses. The researchers also observed that the nine patients in the first group had far lower residual traces of the fungal infection in their blood chemistry, concluding that “the patients who received glucan, in spite of being more seriously ill, had a stronger and more favorable response to therapy.”

Patents Galore in the Decade of the 90’s

The research supporting the claims for Beta-1,3-glucan as an immune system activator has been building steadily with multiple patents filed in the 1990’s by researchers, including Dr. S. Jamas, Dr. D. Easson and Dr. Gary Ostroff, in association with Alpha Beta Technology in attempting to obtain approval for a post operative PPG soluble beta glucan pharmaceutical. While Alpha Beta Technology did not obtain approval in Phase III of the process, much beneficial research was performed during the period by the public corporation.

Several patents associated with the production process of beta glucan and skin care were obtained by Byron Donzis during this period, with a maze of legal entanglements clouding these patents throughout the last decade. Dr. Leonid Ber additionally performed meaningful research during this period involving beta glucan with vitamin C. The immense research findings confirm beta-1,3-glucan produces its multiple broad-scale immune effects by being a nonspecific immune potentiator and modulator. Being a nonspecific immune potentiator, modulator and normalizer means yeast derived isolate beta glucan causes a response capable of being directed to kill many conditions and pathogens.

Dr. Jan Raa, a Norwegian biologist, has been influential in demonstrating the benefits of beta glucan in fish health, including being credited with saving the Norwegian salmon industry in 1990.

Beta Glucan Research in the Now

Major medical school research has been performed at the Department of Microbiology at the University of Nevada School of Medicine under the direction of Kenneth W. Hunter, Jr., Sc.D. and Sally duPre, PhD . The first of multiple patents pending or issued with Dr. Kenneth W. Hunter, Jr. and others, including Frank M. Jordan, have demonstrated microparticulate Beta glucan of 1-4 microns in size and in dosages of 3 – 250 mg or less are preferable in a formulation that must be specially processed to prevent reaggregation (clumping after exposure to water in the digestive process), which in turn significantly enhances immune response normalization, modulation and potentiation.

Dr. Hunter and associate research partners have developed a proprietary process for producing nonaggregated, microparticulate Beta glucan peer-reviewed and designated as MG Glucan, that in test produced a nitric oxide burst in the macrophage cells indicative of microbe killing capabilities significantly greater than that of reaggregated or globular large micron particle size glucans (U.S. Patent 6,476,003). Absorption rates, dosages and the efficacy of small particle microparticulates are the subject of an extensive study on particulate Beta 1,3/1,6 glucan taken orally and processed through the digestive tract into the Peyer’s Patch in the lymphatic system.

Beta glucan research, including adjuvants, vaccines and characteristics, has been sponsored partially by the State of Nevada in conjunction with Nutritional Scientific Corporation, manufacturers of the original NSC-24 oral dietary supplement with Beta glucan which first evolved from the earlier Baylor College of Medicine research on orally administered Beta glucan. Other glucan’ researchers, including Dr. V. Vetvicka and Dr. Gary Ostroff, are exploring Beta glucan in anthrax, vaccines and multiple other conditions, including with clinical studies, in addition to vaccine adjuvant and immunotherapy research directed by Dr. Kenneth W. Hunter, Jr.

Vaclav Vetvicka PhD has supervised extensive Beta glucan research at the University of Louisville while Yihai Cao and his group at the Karolinska Institut in Stockholm, Sweden have been productive, particularly in diabetes research involving beta glucan.

D.L. Williams PhD, I.W. Browder PhD and associates continue with prolific research with Beta glucan at East Tennessee State University and additional educational facilities. G. D. Brown PhD and S. Gordon are active in research at Oxford University in London, UK. David Underhill PhD at Cedars-Sinai Medical Center and William Grossman MD PhD at Biothera are involved in guiding additional beta glucan research. References include multiple double blind, randomized studies under “Pediatrics,” “Pathogens” and many more.

The search for a successful corona-virus vaccine has accelerated research into utilizing beta 1,3/1,6 glucan as a “carrier” to deliver vaccine components and/or pharmaceuticals to a destination site.  The research emphasizes usage of beta 1,3/1,6 glucan as a “conjugate” or hollow carrier of the vaccine component.  Gary Ostroff PhD and Kenneth W. Hunter Jr. ScD have been especially influential in research studies.

With the broad range of benefits indicated based on research from the particulate Beta glucan in past years and the future certain to be both exciting and productive, medical science involving Beta glucan should yield both an enhanced quality and quantity of life through science. Additional studies in beta glucan alternative sources and characteristics make the research in beta glucans an essential part of immunotherapy science and products in the immediate and long-range future.  More clinical trials are anticipated to bring beta glucan into being recognized worldwide for health benefits in a safe delivery form when internalized orally.

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The Beta Glucan Research Organization is not a commercial entity. 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.  The Beta 1,3/1,6 glucan utilized in indexed research studies is sourced as to manufacturer, provider and amounts used solely by the research participants with no input or association by The Beta Glucan Research Organization.

Note on various Glucan forms: Beta 1,3/1,6-D glucan is a baker’s yeast-derived beta glucan with a Beta 1,6 linkage (4-8%) and the molecule skewed to the right. MG Glucan is a specially processed proprietary isolate form of microparticulate Beta 1,3/1,6 glucan that is uniform homogeneous and non-aggregated/non-agglomerated purified Beta 1,3-D glucan that does not 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).

“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, minimally effective in immune potentiation and 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 of the marketing entity.

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