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An intricate network of cells, tissues and organs, the immune system is at the core of defining “self” and protecting the body from harm. Compromised nutritional status can hinder the operations of this on-call protection, just as many specialty compounds can promote healthy function and modulate its interactions.

From the time of conception, the body develops methods of self preservation despite external and internal toxins. At its core, immunity is simple. The body discriminates between what is “you” (autologous or self) and “not you” (foreign or non-self). Approaches to helping the immune system can either boost (generally or specifically) a depressed immune system or mediate the immune response. Suppressed immune response can lead to infectious disease, while hyper-stimulated immunity is related to allergies or autoimmune problems.

“The field of immunology has changed dramatically in the last 20 year s , due in large part to the unique pathophysiology of the HIV virus,” said Omar Cruz, professional educator, Gaia Herbs. “The introduction of such a devastating disease has forced the medical community to focus on maintaining wellness during chronic illness. This concept had already been developed in the theories of preventive wellness and may have in fact reinforced the wellness movement. We’re also seeing an increased prevalence of autoimmune disorders, which is bringing focus onto the delicate balance between immune function and dysfunction.”

Increased media attention on these conditions and the rise of pandemic diseases (i.e., SARS, bird flu) have combined with other factors to increase awareness of the importance of immune support. “The concern for maintaining proper health and immunity is at the forefront of most people’s minds when considering the high cost of health care, loss in production and pay due to untimely illnesses, and their concern for the health of family, friends and co-workers,” said Dawn Phimister, marketing coordinator, EcoNugenics. “The growing base of research and knowledge is empowering individuals to realize they can play a role in maintaining their health and be proactive in the maintenance of that health.”

Larry Robinson, Ph.D., vice president of scientific affairs, Embria Health Sciences, agreed with the assessment. He said: “Consumers have gone from thinking of immune health products as only needed for support during cold and flu season to realizing that all aspects of human health are profoundly affected by the immune system. Since the immune system is responsible for balancing pro-inflammatory and anti-inflammatory responses, an improper immune response can lead to various illness—not only colds and flu, but over time to chronic diseases.”To start the conversation with consumers, it helps to understand the basics behind how the body’s immune system works. The immune system includes white blood cells (leukocytes, produced by stem cells in the bone marrow) and the lymphoid organs (including the thymus gland, lymph nodes, spleen and Peyer’s patches). It responds to infectious attack or internal mutation through both non-specific and specific immunity.

Non-specific immunity, a.k.a. innate or passive immunity, includes the skin and mucosal surfaces lining the respiratory and digestive tracts; those mucosal surfaces contain defense cells such as macrophages and neutrophils, as well as many types of immunoglobulins— antibodies that determine which non-self organisms are pathogenic and which are innocuous. The cells and products of the innate immune system influence the antibody and T cell responses of the adaptive (e.g., active or specific) immune system. Two types of lymphocytes—B cells and T cells—are at the core of adaptive immunity. (One other type of lymphocyte is the natural killer, or NK, cell. This cell is non-specific but active in seeking out tumor or virally infected cells.) B cells are produced in the stem cells of bone marrow and oversee humoral immunity, the link to antibody reaction. T cells are also produced in bone mar row but are sensitized in the thymus, and are at the basis of cell-mediated immunity, responding to the body’s own cells that have changed in response to a viral invasion or cellular mutation. There are several types of T cells, though the cytotoxic and helper T cells are best known. Cytotoxic T cells release lymphotoxins to cause cell death and attract macrophages to clean up the area, and helper T cells, known as CD4 or CD8 cells, stimulate the activity of cytotoxic T cells.

“If the immune system is strong and healthy, the lymphocytes can destroy intruding antigens with the efficiency of an elite, well-trained team of Army Special Forces,” said Hank Cheatham, director of sales and mar keting, Quality of Life Labs .

“Maintaining a healthy immune system provides a much greater chance of long-term health than hoping a therapy will be able to persevere in the face of literally millions of diseased cells degenerating the body.”

One of the biggest factor s impacting immune function is simple nutritional status, something that can be initially addressed with a good multivitamin/mineral product. “Nutrient status is an important factor contributing to immune competence,” wrote researchers from the University of Southampton, England.¹ “Undernutrition impairs the immune system, suppressing immune functions fundamental to host protection. Undernutrition leading to impairment of immune function can be due to insufficient intake of energy and macro nutrients and/or due to deficiencies in specific micronutrients. Often, these occur in combination.” These findings were e choed by researchers at Cornell University, New York, who noted there is particular concern about undernutrition in children, which can weaken the immune response—possibly throughout the course of life.²

“Nutrition authorities have long acknowledged the importance of macronutrients in maintaining the body’s defenses,” said Marci Clow, MS, RD, senior director of technical services, Rainbow Light. “Scientists are now also acknowledging the role micronutrients— vitamins, minerals and related cofactors—play in the support of the immune system. While eating a healthy whole food diet does indeed provide many of the vitamins and minerals necessary for building optimum immune health, the reality is the majority of Americans do not regularly indulge in a ‘healthy whole food diet’.”

“Marginal nutrient deficiencies in the diet can weaken the immune system,” Phimister noted. “ These deficiencies do not cause obvious symptoms of disease, but they can affect mental abilities, coping abilities and the body’s ability to resist disease and infection.”

Perhaps best-known to consumers in the immune support arsenal is vitamin C. This antioxidant neutralizes free radicals and regenerates vitamin E, reducing the burden on leukocytes.³ It also increases production of white blood cells, levels of antibodies and production of interferon, and assists functioning of specific immune cells. While there remains some debate about vitamin C’s ability to prevent the common cold,⁴ it may help prevent pneumonia in some populations.⁵

“Since humans are one of the few animals that do not synthesize vitamin C in their bodies, it is important to ensure you receive plenty of vitamin C through diet and nutritional products,” said Angelica Vrablic, Ph.D., manager of nutrition research at American Health®. “American Health’s Ester- C® is a good example of an advanced form of vitamin C that is non-acidic, quickly absorbed due to the presence of metabolites and has a unique chemical structure that promotes absorption and delays excretion of vitamin C.” Ester-C is made using a proprietary, water-based manufacturing process that results in a pH neutral product with naturally-occurring vitamin C metabolites. In vitro work has found Ester-C can increase the levels of vitamin C within immune cells,⁶ while an unpublished human trial found subjects receiving Ester-C had increased vitamin C level s in the body for up to 24 hour s, suggesting the patented form helps promote absorption and delay excretion of the valuable compound. In addition, a 2002 study involving 180 British subjects found Ester-C supplementation could prevent the common cold, as well as limit severe symptoms and shorten the duration.⁷

There are several other important vitamins for immune health. Vitamin A, for example, is required for adaptive immunity and plays a role in the development of B and Th cells; vitamin A deficiency impairs innate immunity by impeding regeneration of mucosal barriers and diminishing the function of white blood cells.⁸ Another fatsoluble vitamin, vi tamin E, works to help differentiate T cells in the thymus, inducing higher differentiation for greater cellular immunity.⁹ It also appears to improve age-related T cell signaling¹⁰ and NK cel l activity.¹¹ Clinical studies have found higher levels of serum vitamin E may help maintain immune response among the elderly,¹² and that supplementation (200 IU/d) in elderly adults could protect against upper respiratory tract infections and reduce the rate of multiple infections.¹³

The B vitamins are also important to the health and growth of immune cells and antibodies. Deficiency of vitamin B6 has been linked to decreased production of lymphocytes and IL2, a protein cytokine that stimulates the proliferation of T cells (CD4).¹⁴ Folic acid may help increase proliferation of T cells and their ability to produce cytokines.¹⁵ “Scientific data has suggested B-complex deficiencies may occur during chronic stress as well as depression, and this implication provides an interesting correlation to the mind/body connection with immune health and overall well-being,” Cruz added. Minerals also aid immune function.

Selenium is an essential component of thyroid metabolism and antioxidant defense, as well as immune function. It may improve activation and proliferation of B- lymphocytes and enhance T-cell function.¹⁶ It is also involved in several key metabolic activities through its selenoprotein enzymes that protect against oxidative damage.¹⁷ Further, selenium deficiency may allow invading viruses to mutate and cause longer-lasting, more severe illness.¹⁸ Animal research has shown selenium and vitamin E have synergistic effects, enhancing the body’s response to bacterial¹⁹ and parasitic infections.²⁰

Zinc helps to regulate a wide variety of immune system activities, helping the body fight infections and heal wounds. Severe zinc def iciencyimpairs immune function; however, studies now show even mild zinc deficiency may impact immune function by decreasing lymphocyte proliferation and the secretion of IL-2.²¹ Thymus atrophy and compromised cell- and antibody-mediated responses are the “immunological hallmarks” of zinc deficiency.²²

“Typically, individuals seek out zinc as the most needed for immune sys tem benefits,” said Max Motyka, director, human nutrition, Albion Advanced Nutrition. “Of course, zinc is a very important component with a wide range of functions in support of the immune system, playing key roles in many  humoral as well as cell-mediated immune functions.”

Complex carbohydrates also have important roles in immune support. Consider inositol hexaphosphate (IP6), also known as phytate, a naturally polyphosphorylated carbohydrate found in beans, grains and other high-fiber foods. It is important in regulating cellular functions including cell proliferation and differentiation, and has antioxidant properties. Researchers have noted IP6 may enhance immune function by reducing cell pro life ration and contributing to destruction of malignant cells.²³ It affects IL-8 secretion and other neutrophil functions,²⁴ in addition to promoting inflammatory cell secretions.²⁵

The polysaccharide beta-glucan is found in many dietary supplements as beta-1,3/1,4 glucans, which occur primarily in grains such as oats and barley, and beta-1,3/1,6 glucans , primarily derived from yeasts and some varieties of mushrooms (some of which also contain beta-1,6/1,3 glucans). Betaglucans activate macrophage activity without over-stimulating cell mediated immuneresponse.

Yeast-derived beta-glucans (as WGP® 3-6, from Biothera) have been demonstrated to significantly enhance the immune response. WGP 3-6 is taken up in the digestive tract and utilized by the body to increase activity of macrophages and neutrophils.²⁶ Animal research further suggests administration of WGP 3-6 can enhance recovery after bone marrow injury²⁷ and stimulate macrophages without inducing pro-inflammatory cytokines.²⁸

“An immune priming compound such as WGP 3-6 optimizes the performance of immune cells,” said Richard Mueller, president and chief executive officer (CEO), Biothera. “When WGP 3-6 binds to certain white blood cells, it activates these cells to locate and identify an immune challenge faster and kill it more effectively. It makes the existing immune cells ‘battle ready’ without stimulation so when they encounter a foreign challenge they more quickly engage and destroy that challenge.”

Natural beta-glucans and synergistic immune-balancing metabolites produced by yeast in a patented fermentation process are found in Embria’s ingredient EpiCor®, which Robinson said works to support mucosal immunity, increase cytotoxicity of NK cells and inhibit inflammation. “This product helps balance the immune system and keeps it ‘tuned up’ to give proper immune response depending on the type of situation,” he said. “EpiCor appears to naturally ‘educate’ the immune system by helping to balance proper immune response.”

Medicinal mushrooms are naturally rich sources of beta-glucans. “These beneficial mushrooms have been used in the Orient for hundreds of years,” said Phimister, whose company supplies specialty mushroom formulas for immune enhancement. “And the immune modulators found in the beta-glucan molecules in beneficial mushrooms per form three functions: the inducer component is basic training for the immune system, the antigen-specific part helps identify critical features of an infectious enemy, and the suppressor fraction is able to calm the immune system after the ‘enemy’s’ defeat.”

In vitro studies have found maitake (particularly the Dfraction portion) can decrease activation of B cells and activate helper T cells, enhancing cellular immunity, while also increasing cytokine production;²⁹ further studies have found D-fraction also activates macrophages and NK cytotoxicity.³⁰ Dfraction administered to healthy animals has been found to enhance both innate and adaptive immune function;³¹ studies have also found D-fraction increased the survival rate of animals treated with Listeria monocytogenes by enhancing macrophage function³² and inhibiting the activity of hepatitis B virus.³³

“Maitake is traditionally an adaptogenic herb valued for its reputation to promote wellness, vitality and longevity,” said Ron Udel l, president, Sof t Gel Technologies, supplier of Mai take BetaPreme®. “Today, this mushroom is recognized for its beta-glucan content; our pulverized extracts contain high levels of immune-supporting beta-glucans and maintain the nutritional profile and natural fiber content of the original fungus.”

Reishi , called the “mushroom of immortality” in China, may work by increasing CD4 and T cell counts. Shiitake may activate macrophages as well as increase IL-1 production, B lymphocyte proliferation and antibody production. And Agaricus blazei (Himematsutake) may activate macrophages and neutrophils,³⁴ and increase activity of cytotoxic T cells.³⁵

“Researchers have observed that Agaricus blazei mushroom modulates the immune system,” said Yori Takeda, Atlas World USA. “Our Agaricus Bio® supplies immuno-nutrients such as 1,3- and 1,6-beta-glucans, minerals, vitamins, amino acids and enzymes to help maintain a healthy immune system and improve immune response naturally and effectively.”

AHCC ® (Active Hexose Correlated Compound), a proprietary co-cultivation of organically-grown medicinal mushrooms, has been extensively studied for its impact on immune function. Its active ingredients include acetylated alpha-glucan and beta-glucan, and it has an extremely low molecular weight, which promotes bioavailability.

Recent studies have found AHCC is a “potent immuno-enhancer”, working to enhance spleen cell proliferation and cytokine production.³⁶ Animal studies show AHCC can increase survival and clearance of bacteria in a model of surgical tissue infection;³⁷ it also increases survival and decreases severity of infection in an influenza model,³⁸ possibly by bolstering innate immunity and boosting NK activity. AHCC may also function as an antioxidant.³⁹

Polysaccharides also contribute to the immune support offered by aloe. A study on a modified Aloe barbadensis polysaccharide (ActiveAloe®, Aloecorp) found it activated macrophage cells and stimulated fibroblast growth.⁴⁰ Another component, the carbohydrate fraction acemannan from aloe vera, activates macrophages and increases the number and function of cy totoxic T cells.⁴¹ It appears to activated endritic cells, ⁴² and increase the activation capacity of macrophages.⁴³

Larch arabinogalactan (LAG), a mixture of several different water-soluble poly saccharides with a range of molecular weights, is sourced from the Western larch (Larix occidentalis). Studies suggest LAG may enhance several aspect s of immune function including stimulating NK cell cytotoxicity and inhibiting tumor cell metastasis.⁴⁴ In addition, clinical studies using ImmunEnhancer™, from Lonza, found the compound could increase proliferation of monocytes, and increase serum level s of properdin, which activates nonspecific immunity.⁴⁵ Fur ther, the study that tracked properdin levels found LAG had greater individual effects than and synergistic abilities with standardized Echinacea extracts, which also contain arabinogalactans.

Beneficial Botanicals

As mentioned, Echinacea has been studied for its ability to bolster immune system function, particularly when treating common colds and upper respiratory tract infections. Echinacea is the genus for several plants, including E. purpurea, E. angustifolia and E. pallida. It may activate lymphocytes to scavenge for cellular debris and bacteria, and may enhance cell-mediated immunity. High concentrations of Echinacea components have been found to stimulate phagocytic activity, enhancing the release of cytokines.⁴⁶ It also appears to activate macrophages, stimulating proliferation of cytotoxic T cells and suppressor T cells.⁴⁷

In humans, the results have been mixed. A meta-analysis on experimental cold infection studies reported use of standardized extracts of Echinacea reduced by half the likelihood of experiencing a clinical cold.⁴⁸ Two Canadian trials found Echinacea supplementation reduced symptom severity in subjects who contracted upper respiratory infections⁴⁹ or common colds.⁵⁰ However, a controversial 2005 study found no benefit to 900 mg/d of E. angustifolia root, administered in three equal doses, to volunteers before or immediately after a viral challenge;⁵¹ herbal experts questioned the study outcome, given the low dosage and use of an extract of angustifolia versus purpurea.

Gaia Herbs has been conducting research on Echinacea in studies sponsored by the National Institutes of Health (NIH) and has made several significant discoveries. Cruz explained: “We have characterized that the class of compounds in Echinacea known as alkamides, also known as Rx-A factors, are not immuno-stimulatory but are immuno-inhibitory and anti-inflammatory. This discovery may further, and more effectively, explain why Echinacea is effective during the onset stage of rhinovirus infections. We have also found that spring-collected aerial portions of Echinacea, when juiced and freeze-dried, contain a stable group of compounds including arabinogalactan proteins and polysaccharides (Rx- P factors) that can increase macrophage activity, therefore improving overall immune efforts.” The company used the research to create two different immune products with Echinacea—Quick Defense includes Rx-A factors with black elderberry and andrographis for short-term use during acute respiratory challenges; Whole Body Defense is designed for long-term support and combines the Rx- P factors with larch arabinogalactan, maitake and astragalus.

In fact, the Chinese adaptogenic herb astragalus has been traditionally used for long-term strengthening of the immune system, and its polysaccharides, flavonoids and saponins have a range of supportive activity. Astragalus works to increase development of T and B cells, and triggers immune cells into an active state. It also enhances the body’s production of immunoglobulin, stimulates macrophages, and helps activate T cells and NK cells.⁵² Animal studies have shown as t ragalus can increas e macrophage superoxide production and proliferation of splenocytes.⁵³

Indian Ayurvedic tradition also has strong adaptogens, paticularly ashwagandha (Withania somnifera), also known as Indian ginseng. Used for more than 3,000 years in indigenous medical systems for anti-inflammatory and astringent properties, as well as serving as a liver tonic, ashwagandha is being studied for a range of immune supportive properties. It may work as an immunoregulator, stimulating generation of cytotoxic T cells and decreasing stress-induced immunosuppression. ^54,55 Further research suggests it may inhibit autoimmunerelated inflammation,⁵⁶ and serveas an antimicrobial/antifungal.⁵⁷

“Ashwagandha is an example of a well-studied adaptogen,” said Vladimir Badmaev, M.D., Ph.D., vice president of scientific and medical affairs, Sabinsa Corp. “This plant has long been used in Ayurveda as a rejuvenative, especially useful in conditions characterized by mental exhaustion, anxiety, depression and chronic disease.”

Similarly, a standardized extract based on the black elderberry, Sambucol®, has shown benefits as an antiviral and inflammatory modulator. Studies on patients with influenza have shown Sambucol can significantly reduce the duration of flu and improve symptoms.^58,59 In vitro work using blood-derived human monocytes further found Sambucol had immuno stimulatory properties, up-regulating inflammatory and anti-inflammatory cytokine production.⁶⁰

Garlic is also reported to stimulate immunity, including macrophage activity and NK cells, and to increase the production of IL-2, TNF and interferon-gamma. It is suggested that several bioactive components, including S-allylcysteine and S-allylmercaptocysteine (formed during extraction of aged garlic extract [AGE]), contribute to garlic’s immunes timulatig properties.^{61, 62} AGE (Kyolic®, from Wakunaga) specifically maintains homeostasis of immune functions. Studies suggest garlic extract can inhibit the growth of oral pathogens, including Streptococcus mutans and P.ginigvalis, ⁶³ and antibiotic-resistant pathogens.^64,65

Wild oregano , relied upon as a therapeutic herb since ancient Greek and Roman times, also shows powerful activity against outside pathogens. Researchers report even minute dilutions of fresh wild oil of oregano have the ability to sterilize septic water, kill bacteria and halt the growth of fungi. Further, a blend of wild oregano oils (Oreganol P73, from North American Herb & Spice) has potent germicidal actions against pathogens including Candida albicans.

The category of “superfruits” offers several ingredients touted for their antioxidant and immune-supporting properties. Noni (Morinda citrifolia) is widely available in the United States and Europe, and the research base is growing on this Polynesian fruit, which reviewers have found to be pharma cologically active and toxicologically safe.⁶⁶ Active constituents appear to include polysaccharide fractions and glycosides.⁶⁷ Recent research has found noni may help inhibit pathogenesis of some types of yeasts,⁶⁸ and induce vessel degeneration andapoptosis in tumors in vitro.⁶⁹

Another superfruit, mangosteen (Garcinia mangostana), is known as the “Queen of Fruits” in Asia; the tropical evergreen tree develops fruits with a fragrant flesh and deep purple rind, which is what yields the power fulxanthones and polysaccharides. It appears these compounds have powerful antibacterial effects, with in vitro activity against a range of antibiotic-resistant bacteria.^70,71 Mangosteen compounds may also help inhibit IgE-mediated histamine release⁷² and inhibit development of preneoplastic lesions.⁷³

“Xanthones have been studied during the last 30 years because these polyphenols have shown many interesting results in vitro concerning anti-inflammation and other beneficial properties,” said Wayne G. Geilman, Ph.D., senior research scientist with Pure Fruit Technologies, which supplies juice supplements including Mango-xan®. “All the traditional uses of nutraceutical juices are based on consistent supplementation, and our products have the potential to serve as immunomodulators.”

Green “superfoods” may also boost immune function. Different preparations of spirulina, for example, have shown the ability to increase macrophage activity, stimulate cytokine and antibody production, increase NK cell activity and activate T and B cells.⁷⁴ Clinical trials have found administration of a hot water extract of spirulina enhanced NK cell function,⁷⁵ while a spirulina-based supplement from Earthrise Nutritionals given to patients with al lergic rhinit is helped inhibit the production of IL-4, modulating the Th profile.⁷⁶ Researchers have also explored specific-fractions of spirulina. Immolina, a high-molecular-weight polysaccharide fraction, appears to activate leukocytes and expression of chemokines, while enhancing production of immunoglobulins and interferon-gamma.^77,78 And studies on phycocyanin, a biliprotein of spirulina, suggests it enhances mucosal immune function and suppresses allergic IgE antibody response.⁷⁶

Chlorella, another microalgae, may help normalize immune response during times of physical stress,⁸⁰ and aid in immune response to opportunistic or bacterial infection.⁸¹ Canadian researchers reported the use of a patented chlorella extract (Respondin®, f rom Ocean Nutrition Canada) enhanced immune response in human subjects by elevating antibody levels associated with the influenza vaccine.⁸²

Combinations of botanicals may offer synergistic benefits. Triphala, a traditional Ayurvedic combination of Terminalia chebula, Terminalia belerica and Emblica officinalis, has a history of use as an internal cleanser, helping to move out stagnation and improve digestion and nutrient assimilation. More recent research has focused on its antioxidant properties and ability to modulate immune function. Animal research found Triphala could prevent noise-stress-induced alterations in cell-mediated immune response and antioxidant status,⁸³ possibly by stimulating neutrophil functions.⁸⁴

Aller-7™ is a proprietary blend of seven standardized herbal extracts from InterHealth Nutraceuticals. “Aller-7 works by building a healthy immune system that does not overreact to allergens that can result in respiratory problems,” said Fiona Taylor, the company’s director of marketing. “It is also well-tolerated and safe to take on a regular and long-term basis.” In vitro, in vivo and human clinical studies have shown the extract can stabilize mast cells⁸⁵ and promote anti-inflammatory, antioxidant and anti-anaphylaxis activities.^86,87 A three-year, multi-center clinical trial further reported patients with allergic rhinitis who received Aller-7 had significant improvements in symptoms, as well as eosinophil count and mucociliary clearance time.⁸⁸

Consumers who are looking for immune support are increasingly turning to the shelves of natural products retailers to bolster their inherent defenses. “The best way to maintain a healthy immune system is adopting a holistic approach that includes a healthy diet, exercise, plenty of sleep, stress management and, as necessary, nutritional supplementation,” Mueller said. “A good multivitamin is always recommended and then use of products that specifically enhance immune function.”

As Cheatham concluded, “Building a healthy immune system is certainly preferable to fighting a disease. The logic parallels the old expression, ‘An ounce of prevention is worth a pound of cure.’”

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