The Immune Miracle – Chapter 6 – Priming: The Next Frontier of Immune Support (and References)

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

Chapter 6

Priming: The Next Frontier of Immune Support

The last chapter outlined some of the steps you can take to protect your body from infections by using diet, exercise, and dietary supplements. A detailed discussion of one particular dietary supplement was intentionally “saved” for its own chapter – that being an overview of the whole-gluco-polysaccharides (WGPs) that have been briefly mentioned throughout previous chapters.

Often, specific WGPs are referred to by their “generic” name of “beta-glucan.” This can pose a problem for consumers wanting to find the right type of supplement to help prime immune system function, i.e. protection from disease and improvement of vigor and quality-of life. Beta-glucan molecules can be extracted from almost any plant source. Yet, some forms extracted from cereal grains may be quite effective at lowering cholesterol, but have no positive benefit on immune system priming.

The specific type of beta-glucan that I am referring to when I use the term WGP is technically a “beta-1,3/1-6-linked polyglucose” which is a polysaccharide (long chain of sugar molecules) found in the cell walls of yeast cells. Purified beta-glucan has been shown in a wide variety of animal and in vitro studies to have general immuno-priming properties. Among its many beneficial effects are macrophage activation, tumor inhibition, and decreased infection rates. Certain WGPs are patented and protected, by more than 40 U.S. patents or patents pending, for general immune system support as well as for general anti-cancer and specific anti-tumor activity.

Commercial “beta-glucan” products are highly variable in their total content of beta-glucan, ranging from highly purified WGP extracts to less purified “mixed” blends of beta-glucan with other polysaccharides, to completely unknown “generic” versions of beta-glucan with suspect purity or potency.

As described in earlier sections, the body’s first line of defense is the “innate” immune system consisting of soluble blood factors (such as cytokines and complement) and the immune cells (monocytes/macrophages, neutrophils, and natural killer cells) that circulate throughout the body and identify and destroy foreign intruders. WGP has been shown to significantly increase the percent of active (“primed”) immune cells and the level of chemical messengers in the blood that regulate the body’s immune response. Because of its highly purified nature, the WGP form of beta-glucan has also been shown to contain significantly more of the molecular 1,3/1,6 glucose linkages that activate immune cells than any other nutritional supplement on the market.

A series of radioactive labeling studies in humans have shown orally administered WGP to be taken up by gastrointestinal macrophages (immune cells that are the body’s first line of defense), and shuttled to reticulo-endothelial tissues and bone marrow. Within the marrow, the macrophages degrade the WGP particles into smaller fragments that are secreted and eventually bound to specific receptors (CR3) on immune cells, priming their defense mechanisms for immediate action when presented with a pathogen.

In a July 2004 issue of The Journal of Immunology, WGP was shown to prime the immune system with increased plasma cytokines (INF-y and TNF-a), which play an important role in regulating the body’s immune response, but without increase in cytokine IL-1 (which can cause the fever, chills, and muscle aches which have been associated with other immune-enhancing supplements, such as echinacea and arabinogalactan).

Maintaining robust immune system function has emerged as a worldwide health concern – with food, beverage, and supplement manufacturers quick to jump on the bandwagon by touting new products to “boost” or “support” or “stimulate” immune function. Given all the “noise” across the immune support category, the challenge for health professionals and consumers alike lies in evaluating the research behind the increasing number of ingredients and products that claim to enhance immune system function.

According to a survey (2008) by IFIC (the International Food Information Council), nearly 90% of North Americans currently consume, or are interested in consuming, foods and beverages that improve immune system function – and many people will have questions about which products are supported by scientific evidence.

Most of the “immune” products on the market are touting immune health claims based on vitamin content. But, just because a product contains some vitamin A or C or E – or minerals such as selenium or zinc (all of which are certainly needed for optimal immune function), it does not mean it has any bearing on whether or not that product would truly “support” immune function, especially when your body might need it most (e.g. following immune suppression by stress, sleep loss, or close contact with sick/infected individuals).

When out of balance (high or low), the immune system not only fails to protect the body from invading pathogens (bacteria and viruses) but can even attack it, the body mistaking its own cells for dangerous pathogens, resulting in autoimmune diseases such as lupus and rheumatoid arthritis. Allergies can result when the immune system is “overactive” and mistakes an innocuous and harmless particle (such as pollen or cat dander) for an invading pathogen. Another side effect of an out-of-balance immune system is chronic low-grade inflammation, which can increase risks for cancer, heart disease, and other chronic diseases related to elevated inflammation.

As described earlier, and worth repeating, is that the human immune system has two “parts” – the innate and the adaptive immune responses. The innate system is fast-acting and is considered the body’s first line of defense against any foreign invaders. The part of the immune system that most people understand to be the “immune response” is the “adaptive” system, which is a very specific, but delayed, response. Each of the two parts of the immune system work and interact with each other to coordinate protection of the body. For example, the innate system includes physical barriers to infection (such as our skin and mucous membranes), as well as chemical barriers (such as acidic environments and enzymes that kill pathogens or prevent their growth). Another part of the innate system includes the “complement” proteins that help to kill pathogens directly (via lysis) or mark them (opsonization) for later destruction (phagocytosis) by specific immune cells (phagocytes). Natural Killer (NK) cells are another important part of the innate system because of their ability to target and kill viral-infected cells and tumor cells.

In concert with the innate system, the “adaptive” portion of the immune system is a delayed response that is dependent on the innate system for activation. Although initially a delayed response, the adaptive system has “memory” – so the second time the body is exposed to the same pathogen, the response is almost immediate. The main adaptive cells are the “T” and “B” lymphocytes, which work together in a coordinated fashion to recognize (and kill) virus-infected cells and also to help activate other cells in the immune system (via chemical signaling by cytokines).

Obviously, having an immune system response that is either under-active or weakened will increase susceptibility to infections and disease. Unfortunately, our immune system is constantly under attack – not only from pathogens, but also from common everyday physical and emotional stress, sleep deprivation, and environmental insults. In attempts to combat these daily “stresses” on the immune system, consumers are bombarded by a dizzying array of pharmaceuticals and nutraceuticals sold as immune “boosters” (which are probably not what most people really need, based on the simple fact that keeping the immune system in a constant state of stimulation would be expected to result in the detrimental side effects associated with overstimulation, and possibly allergies and autoimmune/inflammatory diseases. Immune system function needs to be balanced – not boosted or suppressed.

The specific WGP form of beta-glucan is known to activate or “prime” innate immune cells to perform their primary protection function: increased ability of macrophages to phagocytose, i.e. engulf and destroy foreign challenges when present. It is important to note that WGP does not automatically “stimulate” immune activity; it only activates immune function when a pathogen is present (e.g. tumor, anthrax, influenza, etc.). In contrast, certain plant-derived or fungi-derived polysaccharides (e.g. echinacea, arabinogalactan, reishi/maitake/shiitake mushrooms) are known to immediately stimulate immune activity, irrespective of the presence of pathogens – a situation that can result in inappropriate levels of inflammation and cytokine release leading to fever, chills, and general malaise.

Scientific Support

There exists a wide-ranging and rich body of research on the mechanism and benefits of specific WGP beta-glucans as biological response modifiers (BRMs) against cancer and infectious diseases. Unfortunately, a major problem with many studies of generic or poorly-defined beta-glucans is the unknown nature of the complex mixtures of partially-purified extracts of mushrooms, yeast, and other plant biomass (which can often include compounds that interfere with immune function or cause undesired side effects).

As documented in The Journal of Immunology (2004), researchers from the Memorial Sloan-Kettering Cancer Center and the Department of Immunology at the University of Louisville School of Medicine demonstrated a clear mechanism by which orally-administered WGP beta-glucans enhance tumoricidal (anti-tumor) activity – by activation of granulocytes (neutrophils and eosinophils), monocytes, macrophages, and NK cells. When consumed orally, WGP particles perform much like a “pro-drug” where they are taken up by gastrointestinal macrophages (via the Peyer’s patches in the small intestine) and shuttled to reticulo-endothelial tissues and bone marrow. Within the marrow, the macrophages degrade the WGP and secrete small, soluble, biologically active fragments that bind to CR3 of mature bone marrow granulocytes. Once recruited from the bone marrow by an inflammatory stimulus, these granulocytes with WGP-primed CR3 can rapidly and specifically target tumor cells for destruction.

These data show us the mechanism by which dietary supplementation with WGPs could legitimately be viewed as a novel anti-cancer therapy, by harnessing immune system activity to help destroy existing tumors and maintain the vigilance of tumor surveillance (catching and destroying cancerous cells before they develop into problematic tumors). In some ways, this “immune sensitizing” or “priming” effect of WGP is reminiscent of the activity of monoclonal antibody therapy (Herceptin, Rituxan, Campath-1H, and Erbitux) that is now being used to treat patients with metastatic breast carcinoma, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and metastatic colon carcinoma, respectively. Additional studies have shown that adding WGP beta-glucan to the immune system (via oral or injection routes) can help to leverage the body’s existing immune mechanisms to target any pathogen or tumor cell.

It’s important to repeat and emphasize that the term “beta-glucan” can be used to describe a wide rage of polysaccharide molecules derived from yeast, fungi, seaweed, and a variety of cereals and other plants. WGP is a specific (patented) form of beta-glucan that is described as a “linear glucose molecule with a ‘beta-1,3/1,6’ branch point extended by a long beta 1,3 oligosaccharide.” The slight molecular differences between WGPs and other forms of beta-glucan are subtle, but important when it comes to specificity, bioactivity, efficacy, and safety. The U.S. Food and Drug Administration considers yeast-derived WGP (from baker’s yeast = Saccharomyces cerevisiae), to be “GRAS” (Generally Recognized As Safe) because of its long history of safe consumption as part of the food supply. Ongoing FDA-monitored clinical trials are investigating a soluble (injected) version of WGP beta-glucan as an adjunct therapy to chemotherapy in cancer treatment.

As discussed in Chapter 3, it is well-known that any type of “over-stress” may lead to increased susceptibility to upper respiratory tract infections. For example, both physical and psychological stressors can result in measurable immune challenges with reductions in key immune system components, such as neutrophils, natural killer (NK) cells, T cells, and B cells. The net effect of an ongoing immune challenge is a weakened immune system, which often results in URTIs as well in generalized reductions in energy levels, mood, and quality of life. Lifestyle factors, such as improved coping with daily stress and getting adequate hours of nightly sleep, may influence the immune response and improve a range of immune system parameters, including immune cell populations, antibody production, and cytokine response. Biological response modifiers such as WGP are effective at enhancing the innate immune response and improving the microbicidal activity of neutrophils, macrophages, and natural killer cells against a variety of pathogens. In several studies, WGP has been shown to reduce the risk of URTIs after stressful events, as well as reduce postoperative infection rates and shorten intensive care unit stay duration among hospitalized patients.

A recent study published in the Journal of Sports Science and Medicine (2009) showed that WGP beta-glucan is able to reduce URTIs (upper respiratory tract infections) and improve overall mood state in over-stressed subjects. In this study, marathon runners were used as a model of over-stress, with results showing a clear reduction in URTI symptoms in the subjects taking WGP beta-glucan versus those taking a placebo. Subjects also showed a significant improvement in measures of overall health and psychological well-being including reduced fatigue and increased vigor (physical and mental energy). During the course of the four-week treatment period, subjects in both treatment groups, 250mg and 500mg beta-glucan, reported fewer URTI symptoms, better overall health, and a more positive mood state compared to placebo.

A wide range of efficacy studies have been conducted on purified WGP beta-glucan, with results showing convincingly that daily supplements of 250-500mg are able to effectively reduce URTIs (upper respiratory tract infections) and improve mood state (energy/fatigue/vigor) under various conditions of physical and psychological stress. Due to problems with purity and bioactivity, however, it is unlikely that “generic” or “mixed” beta-glucan supplements would generate the same efficacy at such a low daily dose — making it important for consumers and health professionals to look for specific yeast-derived WGP beta-glucans that contain the research-proven “1,3/1,6” branching structure.

Illness and stress impact the immune system in both physical and psychological ways. The ability to naturally prime our immune system function back toward optimal levels of functioning represents both the next frontier of immune system support, and also the next frontier of how we think about our overall wellness and quality of life.

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