GENERAL PHYSIOLOGY OF IMMUNE HEALTH

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1 IMMUNO BENEFITS

2 The latest research in immune system health has shown how new immune cell production can be hindered by aging, which allows for the decreased response to vaccines and increased risk for infection we observe in the elderly (Griffith et. al, 2015). The findings from the research, which focused on the thymus and its production of T lymphocytes and the effect of antioxidants, support the free radical theory of aging and elucidate the benefits of dietary antioxidants as we age. These findings are valuable for understanding how we can support cell-mediated immunity, one arm of immune system health. GENERAL PHYSIOLOGY OF IMMUNE HEALTH The immune system is incredibly intricate. Built to affect beneficial actions such as homeostasis maintenance, the immune system fights off foreign antigens and helps the body rid itself of its nonfunctional or dead cells and tissues. The immune system is made up of two parts: humoral and cellular. The former acts as the system memory, and consists of antibodies. When the body produces an antibody for a given antigen, the humoral system remembers that antigen, thereby producing antibodies more rapidly when it again intrudes. Antibodies are also known as immunoglobulins, and are produced by plasma cells (B-cells) as glycoproteins. The process of memory is how we gain immunity. The latter, cellular, is our natural defense system, which consists of white blood cells. These cells move through our bodies, seeking out the bad - infectious microbes, toxins, etc. Both parts of the system, and the system itself, are dependent on many nutrients for their healthy function. Certain nutrients are known to support the health of certain parts of the system. The popular immune system support nutrients, vitamins C and E, zinc and selenium, support oxidative balance, thereby supporting cellular health and normal immune cell production.* IgG, the major immunoglobulin in blood, is a key factor in humoral response. Vitamin A supports normal white blood cell production and activity, while vitamin B6 supports B and T cell development.* Located on many immune system cells, vitamin D receptors allow D to act as a modulating agent, supporting overall system health.* Some nutrients are more often used to support normal immune health in the face of acute immune system concerns, while others are more well known for ongoing immune system maintenance. Elderberry, maitake mushroom, olive leaf extract and echinacea are more likely to be associated with acute support, while a nutrient like colostrum is associated with both ongoing and acute support.* 1

3 EXPLORING RESPONSES TO ANTIGENS Let s discuss the process of humoral immunity more thoroughly. It involves signals and activations, as well as cell proliferation. Consider the invading foreign antigen. It demands a response. The response requires a cell called an APC, antigen-presenting cell, in combination with either a B or a T cell. As described by Lynn Keegan in Healing with Complementary & Alternative Therapies: When an APC presents the antigen on its surface to a B cell, the B cell is signaled to proliferate and produce binding antibodies meant for the specific antigen. The antibodies may have the important function of complement destruction cascade initiation. When an antibody binds to bacteria or a cell, it becomes immobilized. Serum proteins called complement bind to the antibody to destroy the bacteria in the cascade process. Antibodies also have the capability to send the kill signal to natural killer cells and macrophages, which will then take the action of destroying the infected cells. When an APC presents the antigen on its surface to a T cell, the T cell will become activated. Two types of cells, CD4+ and CD8+, have different reactions to that activation. In the case of CD4+ cells, they proliferate and become secretory. In the case of CD8+, or cytotoxic, cells, they kill target cells that specifically express the presented antigen. The CD4+ helper subset of T cells act as regulation for both antibody production and the activity of the CD8+ cells, through the CD4+ cells ability to provide the CD8+ cells with growth factors or signals to proliferate. The secretory substances are critical to the activation of the natural killer cells, macrophages and CD8+ (cytotoxic) cells (Keegan, 2001, p. 410). THE NEED FOR BALANCE BETWEEN TH1 AND TH2 The hormonal messengers responsible for a variety of the biological functions and effects of the immune system, cytokines, can be divided into two categories: pro-inflammatory and anti-inflammatory. However, the anti-inflammatory cytokines still promote allergic response. 2

4 T lymphocytes are a major source of these messengers. Like cytokines, they can also be divided into two categories in this case, the two main subsets previously discussed, CD4 and CD8. The subset CD4 can also be divided into two groups, Th1 and Th2. While Th1 produces pro-inflammatory responses, Th2 is the mechanism that balances this response by producing cytokines such as interleukins 4, 5, 13 and especially interleukin 10. Th1 cells are part of cell-mediated immunity (involves cytokine release, but not antibodies), and Th2 cells mediate the humoral (antibody-mediated) response. It appears that Th2 domination would be favorable. In reality, if there is an excess of Th2, its responses can counteract the Th1-mediated actions that are necessary for immune system health. Therefore, the best case scenario is an established balance of Th1 and Th2 responses to suit the challenge to the immune system (Berger, 2000, p. 424). The role of stress on the balance of Th1/Th2 has been postulated as well. Both glucocorticoids and CAs, through inhibition and stimulation of type 1 and type 2 cytokine secretion, respectively, cause selective suppression of cellular immunity and a shift towards Th2-mediated humoral immunity. This is substantiated by studies showing that stress hormones inhibit the effector function of cellular immunity components the activity of NK cells, Tc cells and activated macrophages. (Elenkov & Chrousos, 1999). HOW IMMUNO BENEFITS SUPPORTS A HEALTHY, BALANCED IMMUNE SYSTEM* Supporting a healthy immune system means supporting both parts of that system, humoral and cellular. Immuno Benefits is aimed at providing the most potent immune supportive nutrients both on a daily basis as well as during acute immune stress. *Because these ingredients support healthy immune function, those with hyperactive immune responses may also benefit from this formula. * The researched ingredients in Immuno Benefits include the yeast beta 1,3/ 1,6 glucan derived from the cell wall of a proprietary strain. Wellmune is a natural way to support immune system health. It has been studied for its effects on respiratory tract infections, moods during stressed states, and immune response after exercise ( Wellmune Clinical Research Wellmune : Natural Immune System Booster, n.d.). Beta-glucan has also been found to play a modulating role in Th1/Th2 balance (Kirmaz, Bayrak, Yilmaz, & Yuksel, 2005). In 2008, one study demonstrated the impact that Wellmune beta glucan had on upper respiratory tract health of wildland firefighters. This was a single blind, random cross-over design wherein subjects consumed either the beta glucan supplement (ßG) or the placebo (P) daily for 14 days, followed by a 3-day wash out period and another 14-day treatment period. Two cross-sectional, non-incentive based health surveys were completed during and at the end of each treatment period. There was a trend for the ßG trial to demonstrate a higer degree of URT health compared to placebo. Perceived overall health was significantly higher in the ßG compared to the placebo trial as well. (Harger-Domitrovich, Domitrovich, & Ruby, 2008). 3

5 In 2009 another study looked at immune functionality during a time of acute immune stress. Forty healthy adult subjects (18 to 65 years of age) were enrolled in a 12-week, randomized, double-blind, placebo-controlled, parallel-group trial conducted during the cold/flu season. The treatment arm compared Wellmune WGP (WGP) gluco polysaccharide (beta-glucan) (500 mg/d) vs a placebo (500 mg rice flour). Cold/flu symptoms were evaluated by medical staff within 24 hours of onset. Quality of Life, assessed by the Physical Component Summary score (SF36v-2), improved significantly in the WPG group vs the placebo group after 90 days as compared to baseline. The WGP group had a significantly lower average fever score than the placebo group (Per Protocol: 0.00 ± 0.00 vs ± 3.42; p = 0.042). No adverse events were detected and no safety concerns were presented. This study suggests 1,3-1,6 beta-glucan from Saccharomyces cerevisiae may modulate and support the immune system. (Feldman et al., 2009). It was found in a study published in European Cytokine Network Journal that after treatment, IL-4 and IL-5 levels in NLF from the Glucan group were found to have decreased significantly. On the other hand, none of the cytokine levels had changed significantly in the placebo group following treatment. Moreover, the percentage of eosinophils in the nasal fluid was found to have decreased significantly after treatment in the Glucan group, while that of the placebo group did not change. (Kirmaz, Bayrak, Yilmaz, & Yuksel, 2005). Another ingredient in Immuno Benefits, Monolaurin, exhibits antiviral and antibacterial activity (Lieberman, Enig, & Preuss, 2006). Also known as glycerol monolaurate, glycerol laurate or 1-Lauroylglycerol, Monolaurin s chemical formula is C 15 H 30 O 4. Researchers have found that Monolaurin can provide broad immune support (Lieberman, Enig, & Preuss, 2006), can combat the toxicity of many gram positive bacteria (Peterson & Schlievert, 2006), and kill Candida albicans (Bergsson, Arnfinnsson, Steingrimsson, & Thormar, 2001). Monolaurin has been found to incorporate itself into the cell membrane of gram positive bacteria, blocking replication and making it an easier enemy for your immune system to take care of (Tokarskyy & Marshall, 2008). Finally, Immuno Benefits contains colostrum. Colostrum supports immune system health through its content of transfer factors.* These molecules can be transferred from a blood donor to a recipient, and can teach the system to recognize antigens, essentially transferring knowledge and memory, and therefore acting as part of the humoral system. When female mammals produce colostrum just after giving birth, that substance supports a newborn s immune system development, getting the process started. Bovine colostrum contains transfer factors like hydrogen peroxide and IgG, which our healthy cells produce to fend off invaders. One nutritional review article looked at the various applications and mechanism of colostrum. They found, It is a complex biological fluid, which helps in the development of immunity in the newborn. It contains significant quantities of complement components that act as natural anti-microbial agents to actively stimulate the maturation of an infant s immune system. Bovine colostrum, a raw material 4

6 for immune milk preparations, can be used to treat or prevent infections of the gastrointestinal tract. It is possible that colostral preparations aimed at specific consumers may play a significant role in healthcare in the future. Besides providing immune support, colostrum has remarkable muscularskeletal repair and growth capabilities. Studies have shown that colostrum is the only natural source of two major growth factors namely, transforming growth factors alpha and beta, and insulin-like growth factors 1 and 2. These growth factors have significant muscle and cartilage repair characteristics. They promote wound healing with practical implications for trauma and surgical patients. Colostral growth factors have multiple regenerative effects that extend to all structural body cells, such as the gut. * Providing that degree of structural support to the gut might also be a potential mechanism for the impact on the immune system. (Uruakpa, Ismond, & Akobundu, 2002). A combination approach to bacterial balance, viral exposure and oxidative stress levels is the best bet for any immune system support regimen. Using nutrients to support your patient s immune health means choosing ingredients that are well-researched and understood to support immunity. It s also important to focus on balance - both oxidative and the balance of Th1 and Th2, while designing an immune support plan. DaVinci s Immune Support Protocol includes both daily support and support for your patient s ability to deal with acute immune system challenges. SUPPLEMENT FACTS Serving Size 2 Capsules Servings Per Container 30 Amount Per Serving % Daily Value Colostrum 500 mg * yielding Immunoglobulins (IgG) 200 mg * Monolaurin 300 mg * Bakers yeast beta glucan 250 mg * *Daily Value not established. Other ingredients: hypromellose (capsule), microcrystalline cellulose, vegetarian leucine. 5

7 REFERENCES Berger, A. (2000). Th1 and Th2 responses: what are they? British Medical Journal,321(7528), 424. doi: /bmj Bergsson, G., Arnfinnsson, J. O., Steingrimsson, O., & Thormar, H. (2001). In vitro killing of Candida albicans by fatty acids and monoglycerides. Antimicrobial Agents and Chemotherapy, 45(11), doi: /aac Elenkov, I. J., & Chrousos, G. P. (1999). Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends in Endocrinology and Metabolism, 10(9), doi: / S (99) Feldman, S., Schwartz, H. I., Kalman, D. S., Mayers, A., Kohrman, H. M., Clemens, R., & Krieger, D. R. (2009). Randomized phase II clinical trials of Wellmune WGP for immune support during cold and flu season. The Journal of Applied Research, (9), Griffith, A.V., et. al. (2015). Metabolic damage and premature thymus aging caused by stromal catalase deficiency. Cell Reports, 12(7), Retrieved from Harger-Domitrovich, S. G., Domitrovich, J. W., & Ruby, B. C. (2008). Effects of an immunomodulating supplement on upper respiratory tract infection symptoms in wildland firefighters. Medicine and Science in Sports and Exercise. doi: /01.mss c1 Keegan, L. (2001). Healing with complementary & alternative therapies. Albany, NY: Delmar. Kirmaz, C., Bayrak, P., Yilmaz, O., & Yuksel, H. (2005). Effects of glucan treatment on the Th1/Th2 balance in patients with allergic rhinitis: a double-blind placebo-controlled study. Eur Cytokine Netw, 16(2), Retrieved from Lieberman, S., Enig, M. G., & Preuss, H. G. (2006). A Review of Monolaurin and Lauric Acid: Natural Virucidal and Bactericidal Agents. Alternative and Complementary Therapies, 12(6), doi: / act Peterson, M. L., & Schlievert, P. M. (2006). Glycerol monolaurate inhibits the effects of gram-positive select agents on eukaryotic cells. Biochemistry, 45(7), doi: /bi051992u Uruakpa, F. O., Ismond, M. A., & Akobundu, E. N. (2002). Colostrum and its benefits: a review. Nutrition Research, 22(6), doi: /s (02) Wellmune Clinical Research Wellmune : Natural Immune System Booster. (n.d.). Retrieved from 6