Demystifying Immune Support

by CP Staff

Supporting a healthy immune response is an important goal as part of an overall program for promoting wellness. The approach to such support, particularly where dietary supplements are concerned, should differ based upon whether the focus is long-term or short-term acute support. Following is a discussion about various internal and external factors that affect the need for long-term and short-term support to immune response, as well as appropriate nutraceuticals to facilitate the support process; but before discussing the factors affecting immune response, a brief review of immune function is in order.

Immune Function: A Brief Review

The body’s natural defenses may be grouped into two broad areas: innate and adaptive. These defenses function to provide the beneficial effects of the immune system, including the ability to counter the effects posed by daily immune challenges. Innate defenses are non-specific, eliciting a general protective response without conferring long-lasting immunity.¹ Adaptive defenses provide a stronger immune response and support immunological memory. After initial contact, each foreign invader can be subsequently identified by a signature antigen, allowing immune responses that are tailored to the specific immune challenge.² Both innate and adaptive responses contain humoral and cellular components. Humoral immunity is so named because it involves substances found in the humours, or body fluids.

Factors Affecting Long-Term Immune Health

Ongoing stress, as opposed to acute stress, is associated with suppression of both cellular and humoral measures of immune function. Aging and health issues may also increase vulnerability to immune challenges during stressors.³ This is consistent with the known decline in immune function during the normal course of aging commonly referred to as immunosenescence.⁴

Poor dietary habits leading to undernutrition or overnutrition also have a negative impact on long-term immune function. While the incidence of undernutrition occurs most frequently in developing countries,⁵ undernutrition can also be a problem in industrialized nations.⁶ Undernutrition can lead to inadequate intake of macronutrients and micronutrients required for proper immune function, resulting in dysregulation of immune responses. Specifically, deficiencies in certain nutrients can impair phagocytic function in innate immunity and adversely affect several aspects of adaptive immunity (e.g., cytokine production, antibody- and cell-mediated immunities).^7-8

Overnutrition occurs when macronutrients are provided in excess of dietary requirements, leading to excessive fat storage and resulting in excess weight gain.⁹ Overnutrition and excess weight have been shown to alter immunocompetence. Being overweight is associated with macrophage infiltration of adipose tissue, which is directly proportional to the degree of being overweight.¹⁰ Furthermore, research has shown that being overweight is associated with impairments in cell-mediated immunity.¹¹

Dietary supplement use for long-term immune support should focus on nutraceuticals that provide ongoing support for daily immune function.

Factors Affecting Short-Term Immunity

Stress has a different effect on short-term immunity. Acute stressors lasting minutes have been shown to be associated with potentially adaptive upregulation of some parameters of natural immunity and downregulation of some functions of specific immunity. Brief stressors, such as exams, tended to suppress cellular immunity while preserving humoral immunity.¹²

Poor diet may also affect short-term immune function,¹³ especially when the overconsumption of sugary foods are common place. The significance of this is that research has shown that in blood drawn from normal human subjects after they consumed glucose, fructose, sucrose, honey or orange juice, neutrophils all had significantly decreased capacity to engulf bacteria.¹⁴ This decrease in immune function may be exacerbated during the colder months (immune response has been shown to be more effective in warmer months).¹⁵

Dietary supplement use for supporting short-term immune health should focus on nutraceuticals that provide immediate support for immune function and/or complementary benefits.

Foundational Nutrients for Long-Term Support

Vitamin C, D and zinc are foundational nutrients that should be used for long-term immune support. Vitamin C plays a profound role in the health of the immune system, promoting the production and function of white blood cells, including leukocytes, neutrophils, lymphocytes and phagocytes.^16-22 In addition, research has demonstrated that supplemental vitamin C supports serum levels of antibodies^23-24 and C1q complement proteins.^25-27 Also, vitamin C has been shown to positively impact interferon levels in vitro,²⁸ and research on supplemental vitamin C suggests that it promotes respiratory wellness in humans.²⁹

Vitamin D is a potent immune system modulator³⁰ with a variety of effects on immune system function that may promote innate immunity.³¹ Furthermore, vitamin D receptors are expressed in several types of immune cells, including monocytes, macrophages, dendritic cells and activated T cells.^32-35 Macrophages also produce the 25-hydroxyvitamin D3-1-hydroxylase enzyme, allowing for local conversion of vitamin D to its active form.³⁶

Zinc is critical for normal development and function of cells that mediate both innate and adaptive immunity.³⁷ Inadequate intake can lead to zinc deficiency and compromised immune responses.³⁸ Deficiency impairs innate immunity (e.g., the complement system, cytotoxicity of natural killer cells, phagocytic activity of neutrophils and macrophages, etc.)^39-40 and adaptive immune function, including lymphocyte number and function.⁴¹ Marginal zinc deficiency, which is more common than severe zinc deficiency, can even suppress some aspects of immune function.³⁸ It is important to remember that zinc is not stored in the body, so regular dietary intake is important for maintaining the integrity of the immune system.

EpiCor®

EpiCor is a product that provides a special fermented form of nutritional yeast. This fermented nutritional yeast is ideal for long-term immune support. In a study evaluating EpiCor, this product was found to promote innate immune response.⁴² This was further documented in a 12-week, randomized, double-blind, placebo-controlled clinical trial,⁴³ where 116 healthy subjects receiving daily supplementation with 500 mg of EpiCor for 12 weeks had significantly better respiratory health. In addition, fermented yeast has been found to support the healthy function of macrophages, granulocytes and NK cells.⁴⁴

Mushrooms

Many mushroom extracts have a history of use in promoting immune response, and are appropriate to use for ongoing, long-term immune support. Such extracts include Agaricus blazei, Cordyceps (Cordyceps sinensis), Maitake (Grifola frondosa), Coriolus versicolor, Reishi (Ganoderma lucidum) and Shiitake (Lentinula edodes). Many are a rich source of naturally occurring polysaccharides, especially beta glucans. These polysaccharides support immune reactions, primarily through modulation of immune responsive cytokines such as IL-1, IL-2, IL-6 and IFN-gamma.^45-52 A good example is Maitake, which has been successfully used as an adjunctive approach for promoting more optimal immune function.^53-54 ImmuneAssist® 24/7 contains all of these mushrooms.

Green Tea

Green tea (Camellia sinensis) extract, also found in ImmuneAssist 24/7, is well known for its antioxidant compounds,⁵⁵ and may help to protect against chromosomal damage to DNA.⁵⁶ In addition, green tea also helps to support healthy, normal cell division.^57-59 A purified form of the EGCG found in green tea is used to make ImmuneAssist 24/7. The EGCG is suspended in a time-released matrix so that it doesn’t break down in stomach acid, allowing much more of this immune-health-promoting compound into the blood stream than can be obtained by drinking green tea.

Nutrients for Short-Term Support

Fucoidan

When support for short-term immune health is desired, fucoidan should be considered.

Fucoidan is a sulfated polysaccharide from brown seaweed. This compound has been shown to support a healthy immune response, promote healthy, normal cell division, and provide protection against inadequate immune response.^60-64 Fucoidan works specifically by production of granzyme A (GzmA), which in turn is believed to trigger the production of cytokines and other immune cells.⁶⁵

Silver

The use of Silver Liquid, a colloidal silver preparation, may complement support for short-term immune health due to its quick effect in interfering with the function of unwanted, foreign invaders^66-68 and without harm to higher animals such as humans.⁶⁹ The silver ion is biologically active and readily interacts with proteins, amino acid residues, free anions and receptors on mammalian cell membranes. Sensitivity to silver by foreign invaders is genetically determined and relates to the levels of intracellular silver uptake and its ability to interact and irreversibly denature key enzyme systems.⁶⁸

Conclusion

Dietary supplement support for healthy immune response can be effective and is advisable. The approach should differ based upon whether the focus is long-term or short-term acute support. For long-term, ongoing support vitamins C and D, zinc, EpiCor and ImmuneAssist 24/7 are recommended. Fucoidan and Liquid Silver are appropriate for short-term immune support.

References

1. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell; 4th Ed. New York and London: Garland Science; 2002.

2. Pancer Z, Cooper MD. The evolution of adaptive immunity. Annual Review of Immunology. 2006;24(1):497-518.

3. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 2004;130(4):601-30.

4. Tortora G, Anagnostakos N. Principles of anatomy and physiology. New York: Harper & Row Publisher; 1981.

5. Food and Agriculture Organization of the United Nations: The state of food insecurity in the world 2006: eradicating world hunger--taking stock ten years after the World Food Summit. Available at: http://www.fao.org/docrep/009/a0750e/a0750e00.htm.

6. Chapman IM: Nutritional disorders in the elderly. Med Clin North Am, 2006;90(5):887-907.

7. Powell J, Borchers AT, Yoshida S, Gershwin ME: Evaluation of the immune system in the nutritionally at-risk host. In: Gershwin ME, German JB, Keen CL, eds. Nutrition and immunology: principles and practice. Totowa, New Jersey: Humana Press, 2000;21-31.

8. Thurnham DI, Northrop-Clewes CA: Effects of infection on nutritional and immune status. In: Hughes DA, Darlington LG, Bendich A, eds. Diet and human immune function. Totowa, New Jersey: Humana Press, 2004;35-64.

9. Schaible UE, Kaufmann SH. Malnutrition and infection: complex mechanisms and global impacts. PLoS Med. 2007;4(5):e115.

10. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219-46.

11. Chandra RK, Kutty KM. Immunocompetence in obesity. Acta Paediatr Scand. 1980;69(1):25-30.

12. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130(4):601-30.

13. Klesges RC, Klem ML, Bene CR. Effects of dietary restraint, obesity, and gender on holiday eating behavior and weight gain. J Abnorm Psychol. 1989;98(4):499-503.

14. Sanchez A, Reeser JL, Lau HS, Yahiku PY, Willard RE, McMillan PJ, Cho SY, Magie AR, Register UD. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr. 1973;26(11):1180-4.

15. Khoo AL, Chai LY, Koenen HJ, Kullberg BJ, Joosten I, van der Ven AJ, Netea MG. 1,25-dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: impact of seasonal variation of immune responses. J Infect Dis. 2011;203(1):122-30.

16. Prinz W, Bortz R, Bregin B, Hersch M. The effect of ascorbic acid supplementation on some parameters of the human immunological defence system. Int J Vitam Nutr Res. 1977;47(3):248-257.

17. Vallance S. Relationships between ascorbic acid and serum proteins of the immune system. Br Med J. 1977;2(6084):437-438.

18. Kennes B, Dumont I, Brohee D, Hubert C, Neve P. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology. 1983;29(5):305-310.

19. Panush RS, Delafuente JC, Katz P, Johnson J. Modulation of certain immunologic responses by vitamin C. III. Potentiation of in vitro and in vivo lymphocyte responses. Int J Vitam Nutr Res Suppl. 1982;23:35-47.

20. Jariwalla RJ, Harakeh S. Antiviral and immunomodulatory activities of ascorbic acid. In: Harris JR (ed). Subcellular Biochemistry. Vol. 25. Ascorbic Acid: Biochemistry and Biomedical Cell Biology. New York: Plenum Press; 1996:215-231.

21. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with imparied neutrophil functions. J Infect Dis. 1996;173(6):1502-1505.

22. Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg AJ. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr. 1980;33(1):71-76.

23. Prinz W, Bloch J, Gilich G, Mitchell G. A systematic study of the effect of vitamin C supplementation on the humoral immune response in ascorbate-dependent mammals. I. The antibody response to sheep red blood cells (a T-dependent antigen) in guinea pigs. Int J Vitam Nutr Res. 1980;50(3):294-300.

24. Feigen GA, Smith BH, Dix CE, et al. Enhancement of antibody production and protection against systemic anaphylaxis by large doses of vitamin C. Res Commun Chem Pathol Pharmacol. 1982;38(2):313-333.

25. Haskell BE, Johnston CS. Complement component C1q activity and ascorbic acid nutriture in guinea pigs. Am J Clin Nutr. 1991;54(6 Suppl):1228S-1230S.

26. Johnston CS, Cartee GD, Haskell BE. Effect of ascorbic acid nutriture on protein-bound hydroxyproline in guinea pig plasma. J Nutr. 1985;115(8):1089-1093.

27. Johnston CS, Kolb WP, Haskell BE. The effect of vitamin C nutriture on complement component C1q concentrations in guinea pig plasma. J Nutr. 1987;117(4):764-768.

28. Dahl H, Degre M. The effect of ascorbic acid on production of human interferon and the antiviral activity in vitro. Acta Pathol Microbiol Scand B. 1976;84B(5):280-284.

29. Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr. 2006;60(1):9-17.

30. Lin R, White JH. The pleiotropic actions of vitamin D. Bioessays. 2004;26(1):21-28.

31. Griffin MD, Xing N, Kumar R. Vitamin D and its analogs as regulators of immune activation and antigen presentation. Annu Rev Nutr. 2003;23:117-145.

32. Brennan A, Katz DR, Nunn JD, et al. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology. 1987;61(4):457-61.

33. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983;221(4616):1181-3.

34. Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys. 2000;374(2):334-8.

35. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab. 1983;57(6):1308-10.

36. Hewison M, Zehnder D, Chakraverty R, Adams JS. Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase. Mol Cell Endocrinol 2004;215(1-2):31-8.

37. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008;14(5-6):353-7.

38. Ibs K-H, Rink L. Zinc. In: Hughes DA, Darlington LG, Bendich A, eds. Diet and human immune function. Totowa, New Jersey: Human Press Inc., 2004;241-259.

39. Kruse-Jarres JD. The significance of zinc for humoral and cellular immunity. J Trace Elem Electrolytes Health Dis. 1989;3(1):1-8.

40. Ibs KH, Rink L. Zinc-altered immune function. J Nutr. 2003;133(5 Suppl 1):1452S-6S.

41. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S-463S.

42. Honzel D, Carter SG, Redman KA, Schauss AG, Endres JR, Jensen GS. Comparison of chemical and cell-based antioxidant methods for evaluation of foods and natural products: generating multifaceted data by parallel testing using erythrocytes and polymorphonuclear cells. J Agric Food Chem. 2008;56(18):8319-25.

43. Moyad MA, Robinson LE, Zawada ET Jr, Kittelsrud JM, Chen DG, Reeves SG, Weaver SE. Effects of a modified yeast supplement on cold/flu symptoms. Urol Nurs. 2008;28(1):50-5.

44. Kovacs DJ, Berk T. Recurrent Clostridium difficile-associated diarrhea and colitis treated with saccharomyces cerevisiae (baker’s yeast) in combination with antibiotic therapy. A case report. J Am Board Fam Pract. 2000;13:138-40.

45. Borchers AT, Stern JS, Hackman RM, et al. Mushrooms, tumors, and immunity. Proc Soc Biol Med 1999;221(4):281-293.

46. Chen YJ, Shiao MS, Lee SS, Wang SY. Effect of cordyceps sinensis on the proliferation of human leukemic U937 cells. Life Sci. 1997;60(25):2349-2359.

47. Ebina T, Fugimiya Y. Antitumor effect of a peptide-glucan preparation extracted from Agarius blazei in a double-grafted tumor system in mice. Biotherapy. 1998;11(4):259-265.

48. Hsieh, TC, Wu, JM. Cell growth and gene modulatory activities of Unzhi (Winds Wunxi) from mushroom Trametes versicolor in androgen-dependent and andro-insensitive human prostata cancer cells. Int J Oncol. 2001;18(1):81-88.

49. Kiho T, Ookubo K, Usui S, et al. Structural features and hypoglycemic activity of a polysaccharide (CS-F10) from the cultured mycelium of Coryceps sinesis. Biol Pharm Bull. 1999;22(9):966-970.

50. Mayell, M. Maitake extrcacts and their therapeutic potential. Altern Med Rev. 2001;6(1):48-60.

51. Wang YY, Khoo KH, Chen ST, et al. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysacharrides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem. 2002;10(4):1057-1062.

52. Wasser SP, Weiss AL. Therapeutic effects of substances ocurring in higher Basidomycetes mushrooms: a modern prespective. Crit Rev Immunol. 1999;19(1):65-96.

53. Yamada Y, Nanba H, Kuroda H. Antitumor effect of orally administered extracts from fruit body of Grifola frondosa (maitake). Chemotherapy. 1990;38:790-6.

54. Nanba H. Immunostimulant activity in vivo and anti-HIV activity in vitro of 3 branched b-1–6-glucans extracted from maitake mushrooms (Grifola frondosa). VIII International Conference on AIDS, Amsterdam, 1992 [abstract].

55. Stoner GD, Mukhtar H. Polyphenols as cancer chemopreventive agents. J Cell Biochem Suppl. 1995;22:169-80.

56. Shim JS, Kang MH, Kim YH, Roh JK, Roberts C, Lee IP. Chemopreventive effect of green tea (Camellia sinensis) amonth cigarette smokers. Cancer Epidemiol Biomakers Prev. 1995;4(4):387-391.

57. Mukhtar H, Ahmad N. Green tea in chemoprevention of cancer. Toxicol Sci. 1999;52(2 Suppl):111-7.

58. Suganuma M, Okabe S, Sueoka N, et al. Green tea and cancer chemoprevention. Mutat Res. 1999;428:339-44.

59. Menon LG, Kuttan R, Kuttan G. Anti-metastatic activity of curcumin and catechin. Cancer Lett. 1999;141:159-65.

60. Kim MH, Joo HG. Immunostimulatory effects of fucoidan on bone marrow-derived dendritic cells. Immunol Lett. 2008;115(2):138-43.

61. Béress A, Wassermann O, Tahhan S, Bruhn T, Béress L, Kraiselburd EN, Gonzalez LV, de Motta GE, Chavez PI. A new procedure for the isolation of anti-HIV compounds (polysaccharides and polyphenols) from the marine alga Fucus vesiculosus. J Nat Prod. 1993;56(4):478-88.

62. Parys S, Kehraus S, Krick A, Glombitza KW, Carmeli S, Klimo K, Gerhäuser C, König GM. In vitro chemopreventive potential of fucophlorethols from the brown alga Fucus vesiculosus L. by anti-oxidant activity and inhibition of selected cytochrome P450 enzymes. Phytochemistry. 2010;71(2-3):221-9.

63. Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, Koh YS, Hyun JW, Park DB, Yoo ES, Kang HK. Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells. Biol Pharm Bull. 2009;32(10):1760-4.

64. Queiroz KC, Medeiros VP, Queiroz LS, Abreu LR, Rocha HA, Ferreira CV, Jucá MB, Aoyama H, Leite EL. Inhibition of reverse transcriptase activity of HIV by polysaccharides of brown algae. Biomed Pharmacother. 2008;62(5):303-7.

65. Hirayasu H, Yoshikawa Y, Tsuzuki S, Fushiki T. Sulfated polysaccharides derived from dietary seaweeds increase the esterase activity of a lymphocyte tryptase, granzyme A. J Nutr Sci Vitaminol (Tokyo). 2005;51(6):475-7.

66. Searle AB. Use of Colloids in Health and Disease. B. Searle, The British Medical Journal, November 1913, p. 83., quoting Dr. Henry Crooks.

67. Jefferson W. Colloidal Silver Today: The All Natural, Wide-Spectrum Germ Killer. Healthy Living Publications; 2003.

68. Lansdown AB. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol. 2006;33:17-34.

69. Lide DR (ed). CRC Handbook of Chemistry and Physics: 80th Edition. Boca Rotan, FL: CRC Press; 1999-2000.