"Glucan (beta-1,3) has been shown to enhance macrophage function dramatically, and to increase nonspecific host resistance to a variety of bacterial, viral, fungal, and parasitic infections." M.L. Patchen, Ph.D. Department of Experimental Hematology and Radiation Sciences Armed Forces Radiobiology Research Institute

"Beta-1,3-glucan, is a potent macrophage stimulant and is beneficial in the therapy of experimental bacterial, viral, and fungal diseases." William Browder, M.D. Department of Surgery and Physiology Tulane University School of Medicine

"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." Joyce K. Czop, Ph.D. Department of Theumatology and Immunology Harvard Medical School

"Glucan was found to be an effective drug in inducing macrophage-mediated destruction in malignant lesions in animals and humans." P. Mansell, M.D. McGill University Cancer Research Unit Victoria Hospital, Montreal, Canada

"Beta-1,3-glucan has been demonstrated to be effective in protecting mice from doses of radiation which are lethal or close to lethal dose." M.L. Patchen Ph.D. Department of Experimental Hematology and Radiation Sciences Armed Forces Radiobiology Research Institute

"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." Nicholas Di Luzio, Ph.D. Department of Physiology Tulane University School of Medicine

Purified Yeast Derived Beta-1,3-D-glucan - A Turly Effective Non-Specific Immune Enhancer

By Leonid Ber, MD

Beta-1,3-Glucan has a long scientific history and a reference list including literally hundreds of papers. Research originated in the 1940's when Louis Pillemer, Ph.D., and his colleagues described a crude yeast cell wall preparation, Zymosan. They reported that this material was able to stimulate non-specific immunity. At that time it was unknown which element of this relatively crude composition, containing a mixture of proteins, lipids and polysaccharides, actually activated the immune response. The answer came later in the 60's, when Nicholas DiLuzio, Ph.D. at Tulane University experimented with Beta-1,3-Glucan. In the late 1980's, Joyce Czop, Ph.D. at Harvard University, described the mode of action of this material in stimulating the immune system: there is a specific receptor for yeast Beta-1,3-Glucan on the surface of certain cells, called macrophages; that when activated, stimulates a cascade of events that turns the body into "an arsenal of defense".

Macrophages play an essential and pivotal role in the initiation and maintenance of the immune response. From an evolutionary point of view, the macrophage is the oldest and most consistently preserved immunologically competent cell known. Not only humans and higher animals, but primitive invertebrates such as Hydra which have no other immunological effector cells, have macrophages. In order to function defensively, the macrophages must pass through a state of activation which involves certain morphological changes. Also, most importantly, a whole sequence of metabolic changes occurs which results in the production of a series of cytokines. They act as internal regulators of the immune system. Activation can be initiated by a variety of different stimuli such as endotoxin, bacteria, viruses or chemicals. However, these activators can be too toxic or pathogenic to be useful. Beta-1,3-Glucan, on the other hand, is orally effective, completely safe and non-toxic, and may be one of the most potent stimulators of the immune response.

There are several different types of Beta Glucan with different levels of activity, the majority of which are inert and used as simple food fillers. The most active type, however, is Beta-1,3-Glucan from the cell wall of yeast. A three dimensional model of this molecule shows it to be a helix, and research at Harvard University has shown that receptors for approximately seven sugar residues exist on the macrophage cell membrane. The fact that such a small number of glucose units can activate these receptors is very remarkable. What is more remarkable still is that there are specific receptors for this sort of polysaccharide chain on the surface of the most ancient cell in the immune cascade. There is now evidence to show that Beta Glucan is, from an evolutionary point of view, the most widely and most commonly observed macrophage activator in nature. The same enhancing mechanisms have been found in all branches of the animal, bird, fish and plant kingdoms.

The activated macrophage is a veritable powerhouse. A macrophage can recognize and kill tumor cells non-specifically, as well as remove foreign debris. It also can produce a number of essential cytokines that are able to stimulate the immune system in general and boost bone marrow production.

Some individuals, because of age, chronic infection or poor nutrition, have a compromised immune defense system. They are susceptible to all of the following problems: arthritis; reduced wound healing capacity; reduced bone marrow proliferation with resulting lowered white cell counts and anemia; increased incidence of cancers; and increased incidence of viral, fungal, and bacterial infection.

It is well understood that one of the main elements of the aging process is a lowering of the effectiveness of the immune function. All of the problems mentioned above occur with aging. In addition, the immune system is impaired by numerous environmental factors such as UV radiation, food preservatives and antibiotics. Physical and emotional stress and intense physical exercise can also negatively affect the immune system. It is well documented that generally healthy athletes frequently suffer from influenza or pneumonia following heavy periods of intense exercise. The same immunosuppression is observed in people with stress-related diseases, such as coronary disease. Under these influences, the number of macrophages available are reduced and unable to participate in the immune cascade, which causes even deeper immunosuppression. Beta-1,3-Glucan has been shown to both stimulate and activate macrophage cells; which will counter these negative effects.

In the 1970's, after extensive studies in animals, human experiments with Yeast Beta Glucan began. In a study conducted by Peter Mansell, M.D., Yeast Beta Glucan was injected into subcutaneous nodules of malignant melanoma. Subsequent biopsies of the injection sites found no evidence of melanoma, just a collection of obviously activated macrophages.

A subsequent study treated a number of women who experienced recurrent malignant ulcers of the chest wall following mastectomy and radiation for breast cancer. After an application of Yeast Beta Glucan, these normally very indolent ulcers healed completely. The same material was used in the treatment of large pressure ulcers at the New Orleans Charity Hospital with complete resolution of the ulcers, some of which went down to the sacrum. An unexpected benefit was the complete lack of infection and the rapidity of the reappearance of normal skin.

The first human study on Beta-1,3-Glucan's systemic effect was in the mid-1980's on advanced HIV infection. Even in these deeply immunologically deficient individuals, an increase in serum cytokines IL-1, IL-2 and interferon was measured.

Results of another clinical trial showed a significant mortality decrease from infectious complications in severe trauma patients.

At the time of these studies, a crude preparation containing Beta Glucan was already registered in Eastern Europe for injection to treat the effects of bone marrow suppression from radiation or chemotherapy.

One of the most remarkable oral studies with Beta Glucan was undertaken by the U.S. Armed Forces Radiobiology Institute. In a well-controlled study, rats were given a lethal dose of radiation. Seventy percent of these rats were completely protected from the radiation effects when given a dose of Yeast Beta Glucan by mouth AFTER the radiation.

Myra Patchen, Ph.D., co-author of the above-referenced study, discovered that Beta Glucan is also a free radical scavenger. It is able to protect blood macrophages from free radical attack during and after the radiation, allowing these cells to continue their important functions in the irradiated body and release factors important to the restoration of normal bone marrow production. Free radical scavenging assays were repeated in different models which confirmed the antioxidant effect. In light of what is known about the potential of free radicals to accelerate aging, cause cancer and other diseases, this particular effect of Beta-1,3-Glucan is especially important.

Recent independent experiments completed at Baylor College of Medicine in the laboratory of Professor Phil Wyde, Ph.D., also indicate the oral effectiveness of Beta-1,3-Glucan in stimulating non-specific immunity. Peritoneal macrophages doubled their phagocyte activity in mice fed with Beta-1,3-Glucan. This systemic effect of oral application is comparable to that achieved by injection, which makes this material a unique and very valuable oral immunostimulant.

When Beta-1,3-Glucan was added to the antibiotic regimen in animals challenged with different bacterial pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli and others) and viral pathogens (Herpes virus), a reduced amount of antibiotics or antivirals was needed to cope with the infection. Beta-1,3-Glucan also has an antifungal effect, shown in experiments with Candida albicans. Such a broad anti-infective spectrum of Beta-1,3-Glucan can be explained only by the fact that the immunostimulation produced by this unique material is non-specific.

Continuing research on the oral application of Yeast Beta-1,3-Glucan revealed that it also increases the effectiveness of other oral cholesterol-reducing agents, such as niacin and Lopid®. Interestingly, recent research has also demonstrated the anti-diabetic effect of IL-1 cytokine, which increases insulin production causing the lowering of blood glucose level. Macrophages are the main source of IL-1 in the body and its production can be boosted by Yeast Beta-1,3-Glucan supplementation. Mindful of the extremely high rate of atherosclerotic complications and the extraordinary requirement for antioxidants in diabetic patients, Yeast Beta-1,3-Glucan is an obvious adjuvant for an improved lifestyle in these conditions.

As is repeatedly shown in the multitude of studies concerning the activity of Beta Glucan as an immune stimulator, or perhaps more descriptive, a "biological defense modifier" there are enormous benefits to be obtained by the use of Yeast Beta-1,3-Glucan as a nutritional supplement.

The aging process has been defined as "the sum total of life's physical embarrassment due to adverse conditions". Yeast Beta-1,3-Glucan may well be the first and only true anti-aging supplement. It is a defense against negative events such as infection, tumors and radiation damage, and adjunctive to the positive effects of antioxidants, lipid balance enhancers, antibiotics and other therapeutics. The result is improved general health which means greater enjoyment of life, fewer infirmities, less time and money required for medical needs and potentially dramatic savings in health-related expenditures over time.

To summarize, Yeast Beta-1,3-Glucan is a safe and very potent nutritional supplement with a systemic effect that can be described as non-specific immune stimulation combined with free-radical scavenging activity. Technically it is a polysaccharide molecule made completely with glucose that is highly purified. Glucose is a simple saccharide that the body transforms to energy as ATP and stores in muscles, liver and other tissues in a form of glycogen. Beta-1,3-Glucan is different from energy storing glucose containing polysaccharides because the connection between the glucose units is different. More specifically, it is the beta-1,3-linkage which makes this compound so unique. It is Generally Recognized As Safe (category GRAS according to FDA) and has no known toxicity or side effects.

Some of the biological events illustrating this stimulation are:

Activation of macrophages, expressing increased nonspecific phagocytic activity allowing macrophages to destroy pathogens more efficiently, frequently preventing disease.

Release of important cytokines such as IL-1, IL-2, among others, which initiates an immune cascade and triggers other cell lines, such as T-cells. Release of colony-stimulating factors, boosting bone marrow production.

Cholesterol-reduction through cell activation and anti-oxidant activity

Many of the people who will benefit from Yeast Beta-1,3-Glucan supplementation are:

1. People with impaired immunity from any cause including, HIV infection; people with high occurrence of infectious diseases, tumors or undergoing chemotherapy and radiotherapy; people over the age of 40 when the natural aging process starts to slow down immune reactivity; geriatric patients, and others with a compromised immune response.

2. People who are affected by extra free-radical production from external sources: such as UV radiation, electromagnetic fields, poor nutritional habits, food preservatives, and people with chronic disease such as diabetes or chronic inflammation.

3. Professional and amateur athletes as well as people who work out intensively. People under physical or emotional stress.

4. People with high risk of atherosclerosis might consider adding Yeast Beta-1,3-Glucan to their diet in addition to any cholesterol-reducing drugs. Macrophage activation helps draw extra cholesterol from the blood, prevent further plaque formation on the arterial walls and phagocytize existing plaque which is recognized as a foreign body.

Beta-1,3-Glucan for Immune System Activation Ever since the 1940s, scientists have been honing their knowledge of the remarkable abilities of a simple substance derived from baker's yeast to effectively stimulate and activate the immune system and to work therapeutically in cancer, ulcers, radiation exposure, infection, and trauma.

The research supporting the claims for beta-1,3-glucan as an immune system activator has been building steadily in recent decades. In 1996 alone, 144 scientific studies were published on the medical uses of beta-1,3-glucan. One fact has consistently emerged from these studies: beta-1,3-glucan produces its multiple broad-scale immune effects by being a nonspecific immune stimulator. This means it causes a response capable of being directed at many conditions, perhaps all.

Research at Harvard University in the 1980s showed that the macrophage-a key immune system white blood cell that "eats" unwanted, foreign microbes-has a specific receptor for beta-1,3-glucan. In nontechnical terms, we might say the yeast talks directly to the immune cell. When the macrophage is activated by this contact, it starts a "cascade of events turning the cells into 'an arsenal of defense,'" explains Donald J. Carrow, M.D., a physician based in Tampa, Florida, who has used beta-1,3-glucan successfully with many patients.

Dr. Carrow 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." 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."

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.

In the mid-1980s, researchers at Tulane University School of Medicine reported that beta-1,3-glucan injected directly into chest-wall 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.

The ingestion produced measurable increases in the production of key immune cell components, Dr. Patchen reported. She also noted that the strongest benefits were observed one day before, one hour before, and one hour after radiation exposure. Dr. 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.

Dr. Patchen further suggested that beta-1,3-glucan appears to work as a free-radical scavenger. She believes it may even protect the macrophages from damage by radiation, toxins, heavy metals, invading microbes, and other poisons (collectively called free radicals) in the body.

When it comes to resisting infections, beta-1,3-glucan's capabilities are well documented. Scientists at the State University of São Paulo in Brazil tested beta-1,3-glucan's ability to stimulate 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. They 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."

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 [a substance that directs immune response] 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.

In his own clinical practice, Dr. Carrow has tested beta-1,3-glucan on a variety of conditions, including cancer and ulcers, and for general health maintenance. Dr. Carrow injected a skin cancer lesion with 10 mg of beta-1,3-glucan and within three months the tumor had completely disappeared, he reports. 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, Dr. Carrow was able to heal them completely within two months.

The information in this brochure is for educational purposes only and is not recommended as a means of diagnosing or treating an illness.