Immune health: Polysaccharides

NK cell activity is one of the many targets of mushrooms, a variety of which have been studied for modulation of both adaptive and innate immune response. Agaricus blazeii Murill has been shown to increase NK cell activity in cancer patients, in addition to increasing IgG levels, stimulating T cell production in the spleen, enhancing phagocytic capability and improving the bodys resistance to bacterial infection.^1,2,3

The mushroom Pleurotus ostreatus may limit the immune suppression caused by sort-term, high-intesnity exercise, according to a 2010 Slovakian trial.⁴ Researchers found during recovery from intense exercise, supplementation with a beta-glucan-rich extract (as Imunoglukan P4H®, from Pleuran s.r.o.) in elite athletes for two months inhibited reductions in NK cell counts and activity that were experienced by athletes taking placebo.

Matiake mushroom (Grifola frondosa) contains beta 1,3/1,6 glucans and can promote cytokine activity and up-regulate certain neutrophils in a dose-dependent manner.⁵ Further, maitake (as D-Fraction®, from Mushroom Wisdom) may activate immune cells, macrophages dendritic cells and T cells, in addition to enhancing the cytotoxicity of NK cells.^6,7 In 2010, Japanese researchers reported a low molecular weight protein fraction from maitake administered to an animal model increased spenocyte proliferation and production of cytokines such as IL1a, TNFa, IL-10, IL-12 and IFN-gamma.⁸ They also noted the fraction activated NK cells, macrophages and dendritic cells.

Reishi mushroom (Ganoderma lucidum) has also generated positive immune research results, such as modulating T-cell activation by acting directly on monocytes; promoting splenic B cell activation and antibody secretion; and stimulating TNF-alpha and IL-6 production and IFN-gamma release.^9,10,11,12 In 2010, Taiwan scientists published results showing reishi proteins can activate macrophages and T cells, while polysaccharides from the mushroom activate macrophages.¹³

The proprietary Active Hexose Correlated Compound (AHCC®, manufactured by Amino Up Chemical Co., U.S. distribution by Maypro Industries), is a polysaccharide-rich mushroom-based ingredient derived from the mycelia of select basidiocymetes. AHCC can modulate both adaptive and innate immunity,¹⁴ including improved response to acute infections, influenza and West Nile encephalitis.^15,16,17 A 2010 publication by Yale School of Medicine researchers outlines the effects of AHCC administration in healthy adults aged 50 years or older.¹⁸ Intake of AHCC increased the frequency of CD4 and CD8 T cell-production of INF-gamma and TNFa. They noted it took at least 30 days of AHCC intake to produce such results, which remained 30 days after discontinuing intervention.

Polysaccharides are central to the actions of several other specialty supplement ingredients on immune function. The yeast Saccharomyces cerevisiae is the source of a couple such ingredients developed for their beta-glucan content.

A proprietary 1,3/1,6 glucopolysaccharide derived from the cell walls of the yeast (as Wellmune WGP®, from Biothera) has been shown to decrease the incidence of URIs in populations prone to experiencing stress-related immune suppression. For instance, firefighters taking Wellmune or placebo for 12 days (followed by a three-day washout period and another 14-day treatment period) were considerably less likely to develop URIs.¹⁹ In another trial, 150 subjects with high-lifestyle stress were randomized to receive placebo, 250 mg/d or 500 mg/d of Wellmune WGP for four weeks;²⁰ fewer subjects taking Wellmune had any type of URI symptoms. Wellmune has also significantly reduced the incidence of URIs in marathon runners.²¹ In other research, healthy adults receiving 250 mg/d of Wellmune WGP or placebo for 90 days had less severe colds and shorter duration than those taking placebo,²² while Wellmune supplementation in children reduced the incidence of fever and eliminated the need for study subjects to miss school due to colds.²³

In 2010, results presented at the 51st Annual Meeting of the American College of Nutrition, New York, showed moderately to high-stress women taking Wellmune experienced fewer cold/flu symptoms and higher energy levels. In the study, 77 healthy women (age 38 +/- 12 years) were pre-screened for moderate levels of psychological stress and given either a placebo or 250 mg/d of Wellmune WGP for 12 weeks. Only 10% of the Wellmune group reported URI symptoms (sore throat, stuffy or runny nose and cough) compared with 29% in the control group.

A high-metabolite immunogen ingredient derived from fermentation of S. cerevisiae (as EpiCor®, from Embria Health Sciences) has made its early mark on cold and flu research. Studies investigating the effects of 500 mg/d EpiCor on cold and flu incidence and symptoms in flu-vaccinated adults have linked decreased incidence of URIs, as well as the duration of symptoms, to Epicor supplementation, when compared to placebo. Additional research on 500 mg/d of EpiCor also showed increased IgA and IgE levels following supplementation. NIS Labs researched this same dose of Epicor in human subjects, finding increased levels of hematocrit and IgA, along with decreases in serum IgE and IL-10. In 2010, University of Michigan Medical Center researchers reported 12 weeks of Epicor supplementation in an at-risk population experienced a reduction in incidence of cold- or flu-like symptoms.²⁴ However, results of the randomized, double blind, placebo-controlled clinical trial also showed no significant reduction on duration or severity of symptoms compared to placebo.

Another type of immunomodulatory polysaccharide is larch arabinogalactan (LAG), extracted from Larix occidentalis. LAG can stimulate NK cell cytotoxicity, induce cytokines and influence monocyte production.^25,26 In one study, LAG (as ResistAid®, from Lonza) selectively enhanced antibody response to a pneumonia vaccine in healthy subjects, without increasing the nonspecific innate immune response.²⁷ ResistAid subjects had increased IgG response, but the intervention had no effect on salivary IgA, white blood cell count, inflammatory cytokines or complement.

Most recently, a randomized, double blind, placebo-controlled, parallel-group pilot study conducted by Medicus Research, Northridge, CA, charted increased antibody response to the 23-valent pneumococcal vaccine in healthy volunteers taking ResistAid, compared to placebo.²⁸ Specifically, volunteers who received ResistAid for 30 days prior to vaccination and up until day 72 had significantly higher pneumococcal IgG levels in two antibodies subtypes (18C and 23F) at both day 51 and at day 72, compared to those who took placebo. Lead investigator Jay Udani, M.D., noted modulating the immune system in direct response to antigenic stimulation rather than nonspecific augmentation represents a more physiologic approach to immune enhancement.

References

1. Chan Y et al. Immunomodulatory effects of Agaricus blazei Murill in Balb/cByJ mice. J Microbiol Immunol Infect. 2007 Jun;40(3):201-8.

2. Bernardshaw S, Johnson E, Hetland G. An extract of the mushroom Agaricus blazei Murill administered orally protects against systemic Streptococcus pneumoniae infection in mice. Scand J Immunol. 2005 Oct;62(4):393-8.

3. Ahn WS et al. Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy. Int J Gynecol Cancer. 2004 Jul-Aug;14(4):589-94.

4. Bobovák M et al. Effect of Pleuran (-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes. Appl Physiol Nutr Metab. 2010 Dec;35(6):755-62.

5.  Wu MJ et al. Immunomodulatory properties of Grifola frondosa in submerged culture. J Agric Food Chem. 2006 Apr 19;54(8):2906-14.

6. Kodama N et al. Enhancement of cytotoxicity of NK cells by D-Fraction, a polysaccharide from Grifola frondosa. Oncol Rep. 2005 Mar;13(3):497-502.

7. Kodama N, Murata Y, Nanba H. Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice. J Med Food. 2004 Summer;7(2):141-5.

8. Kodama N et al. Potential antitumor activity of a low-molecular-weight protein fraction from Grifola frondosa through enhancement of cytokine production. J Med Food. 2010 Feb;13(1):20-30.

9. Jeurink PV et al. Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells. Int Immunopharmacol. 2008 Aug;8(8):1124-33.

10. Lin KI et al. Reishi polysaccharides induce immunoglobulin production through the TLR4/TLR2-mediated induction of transcription factor Blimp-1. J Biol Chem. 2006 Aug 25;281(34):24111-23.

11. Kuo MC et al. Ganoderma lucidum mycelia enhance innate immunity by activating NF-kappaB. J Ethnopharmacol. 2006 Jan 16;103(2):217-22.

12. Silva D et al. Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol. 2009 Oct;9(11):1272-80.

13. Yen CH et al. Polysaccharides PS-G and protein LZ-8 from Reishi (Ganoderma lucidum) exhibit diverse functions in regulating murine macrophages and T lymphocytes. J Agric Food Chem. 2010 Aug 11;58(15):8535-44.

14. Gao Y et al. Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses. Cancer Immunol Immunother. 2006 Oct;55(10):1258-66.

15. Ritz BW. Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. Nutr Rev. 2008 Sep;66(9):526-31.

16. Nogusa S et al. Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutr Res. 2009 Feb;29(2):139-43.

17. Wans S et al. Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice. J Nutr. 2009 Mar;139(3):598-602.

18. Yin Z et al. Effects of active hexose correlated compound on frequency of CD4+ and CD8+ T cells producing interferon- and/or tumor necrosis factor- in healthy adults. Hum Immunol. 2010 Dec;71(12):1187-90.

19. Harger-Domitrovich SG et al. Effects of an Immunomodulating Supplement on Upper Respiratory Tract Infection Symptoms in Wildland Firefighters. Presented at the Annual Meeting of the American College of Sports Medicine, May 2008.

20. Presented at the American College of Nutrition Annual Meeting, Sept 2007.

21. Talbot S and Talbot J. Effect of Beta 1, 3/1, 6 Glucan on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes. J Sports Sci and Med. 2009;8:509-515.

22. Feldman S et al. Randomized Phase II Clinical Trials of Wellmune WGP® for Immune Support During Cold and Flu Season. J Applied Res. 2009;9(1,2).

23. Feldman S et al. Randomized Phase II Clinical Trials of Wellmune WGP® for Immune Support During Cold and Flu Season. J Applied Res. 2009;9(1,2).

24. Moyad MA et al. Immunogenic yeast-based fermentate for cold/flu-like symptoms in nonvaccinated individuals. J Altern Complement Med. 2010 Feb;16(2):213-8.

25. Kelly GS. Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide. Altern Med Rev. 1999 Apr;4(2):96-103.

26. Currier NL, Lejtenyi D, Miller SC. Effect over time of in-vivo administration of the polysaccharide arabinogalactan on immune and hemopoietic cell lineages in murine spleen and bone marrow. Phytomedicine. 2003 Mar;10(2-3):145-53.

27. Presented at the 50th Annual Meeting of the American College of Nutrition in Orlando, Fla., October 2009.

28. Udani JK et al. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers. Nutri J. 2010;9:32.