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Immunomodulatory dietary polysaccharides: a systematic review of the literature

Jane E Ramberg, Erika D Nelson, Robert A Sinnott

Nutrition Journal · 2010 · Systematic review

doi:10.1186/1475-2891-9-54

Abstract

Background. A large body of literature suggests that certain polysaccharides affect immune system function. Much of this literature, however, consists of in vitro studies or studies in which polysaccharides were injected. Their immunologic effects following oral administration is less clear. The purpose of this systematic review was to consolidate and evaluate the available data regarding the specific immunologic effects of dietary polysaccharides.

Methods. Studies were identified by conducting PubMed and Google Scholar electronic searches and through reviews of polysaccharide article bibliographies. Only articles published in English were included in this review. Two researchers reviewed data on study design, control, sample size, results, and nature of outcome measures. Subsequent searches were conducted to gather information about polysaccharide safety, structure and composition, and disposition.

Results. We found 62 publications reporting statistically significant effects of orally ingested glucans, pectins, heteroglycans, glucomannans, fucoidans, galactomannans, arabinogalactans and mixed polysaccharide products in rodents. Fifteen controlled human studies reported that oral glucans, arabinogalactans, heteroglycans, and fucoidans exerted significant effects. Although some studies investigated anti-inflammatory effects, most studies investigated the ability of oral polysaccharides to stimulate the immune system. These studies, as well as safety and toxicity studies, suggest that these polysaccharide products appear to be largely well-tolerated.

Conclusions. Taken as a whole, the oral polysaccharide literature is highly heterogenous and is not sufficient to support broad product structure/function generalizations. Numerous dietary polysaccharides, particularly glucans, appear to elicit diverse immunomodulatory effects in numerous animal tissues, including the blood, GI tract and spleen. Glucan extracts from the Trametes versicolor mushroom improved survival and immune function in human RCTs of cancer patients; glucans, arabinogalactans and fucoidans elicited immunomodulatory effects in controlled studies of healthy adults and patients with canker sores and seasonal allergies. This review provides a foundation that can serve to guide future research on immune modulation by well-characterized polysaccharide compounds.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 21, 2026. Paragraph numbers are ours, so an answer can point at one.

Background

Polysaccharide-rich fungi and plants have been employed for centuries by cultures around the world for their dietary and medicinal benefits. Often thought to merely support normal bowel function and blood glucose and lipid levels, certain polysaccharides have attracted growing scientific interest for their ability to exert marked effects on immune system function, inflammation and cancers. Many of these chemically and structurally diverse, non- to poorly-digestible polysaccharides have been shown to beneficially affect one or more targeted cellular functions in vitro, but much of the in vivo literature consists of studies in which polysaccharides were injected. For clinicians and scientists interested in immunologic effects following dietary intake, the value of such studies is uncertain. Polysaccharides that elicit effects in vitro or by injection may be ineffective or have different effects when taken orally. We thus decided to conduct a systematic review to evaluate the specific immunologic effects of dietary polysaccharide products on rodents and human subjects.

Literature review

Studies were identified by conducting electronic searches of PubMed and Google Scholar from their inception to the end of October 2009. The reference lists of the selected articles were checked for additional studies that were not originally found in the search.

Study selection and data extraction

The following search terms were combined with the term polysaccharide: dietary AND immune, or oral AND immune, or dietary AND inflammation, or oral AND inflammation. When specific polysaccharides or polysaccharide-rich plants and fungi were identified, further searches were conducted using their names with the same search terms. Studies were selected based on the following inclusion criteria:

1. Rodent or human studies

2. The presence of test group and control group (using either placebo, crossover, sham, or normal care)

3. Studies reporting statistically significant immunomodulatory effects

4. English language

5. Studies published up to October 2009.

Two researchers (JER, EDN) reviewed the list of unique articles for studies that fit the inclusion criteria. Uncertainties over study inclusion were discussed between the researchers and resolved through consensus. Searches were then conducted to obtain specific polysaccharide product information: safety (using the search terms: toxicity, NOAEL, LD50), composition and structure, and disposition.

Quality assessment

Each study was assessed as to whether or not it reported a significant outcome measure for the polysaccharide intervention group.

Results

A total of 62 rodent publications (Tables 1, 2 and 3) and 15 human publications (Table 4) were deemed appropriate for inclusion in this review. Available structural and compositional information for these immunomodulatory polysaccharides are provided in Table 5 and safety information is provided in Table 6. The majority of animal studies explored models in which animals were injected or implanted with cancer cells or tumors, were healthy, or were exposed to carcinogens. Other studies investigated immunodeficient, exercise-stressed, aged animals, or animals exposed to inflammatory agents, viruses, bacterial pathogens, pathogenic protozoa, radiation or mutagens. Human studies assessed immunomodulatory effects in healthy subjects, or patients with cancers, seasonal allergic rhinitis or aphthous stomatitis. Because of the limited number of human studies, we included some promising open-label controlled trials. Human study durations ranged from four days to seven years; daily doses ranging from 100-5,400 mg were reported to be well-tolerated.

A number of studies in healthy human adults demonstrated immune stimulating effects of oral polysaccharides. Arabinogalactans from Larix occidentalis (Western larch) were shown in RCTs to increase lymphocyte proliferation and the number of CD8+ lymphocytes and to increase the IgG subtype response to pneumococcal vaccination. A furanose extract from Panax quiquefolium (North American ginseng) was shown in an RCT of healthy older adults to decrease the incidence of acute respiratory illness and symptom duration. Finally, an RCT of healthy adults consuming Undaria pinnatifida (wakame) fucoidans found both immune stimulating and suppressing effects, including increased stromal-derived factor-1, IFN-g, CD34+ cells and CXCR4-expressing CD34+ cells and decreased blood leukocytes and lymphocytes.

Studies in healthy animals showed a number of immune stimulating effects of various glucan products from Agaricus subrufescens (A. blazei) (aqueous extracts, aqueous extracts with standardized β-glucans, α-1,6 and α-1,4 glucans, and whole plant powders); Lentinula edodes (shiitake) (lentinan and β-glucans); Saccharomyces cerevisiae (β-1,3-glucans); Laminaria digitata (laminarin); Sclerotium rofsii (glucan phosphate); Sclerotinia sclerotiorum (SSG); and Phellinus linteus (powder and aqueous, alcohol-precipitated extract). A furanose extract from P. quiquefolium and pectins from Buplerum falcatum and Malus (apple) spp. have also been shown to enhance immune function in healthy young animals. Cyamopsis tetragonolobus galactomannan (guar gum) or highly methoxylated pectin feeding exerted numerous stimulating effects on antibody production in older animals.

Evidence for the effectiveness of oral polysaccharides against infection and immune challenges has been mainly demonstrated in animals. Immune stimulating effects have been shown in resting and exercise-stressed animals with thioglycollate, clodronate, or HSV-1 injections fed Avena (oat) spp. soluble glucans; animals injected with or fed E. vermiformis and fed Avena spp. particulate glucans; animals with E. coli injections fed L. digitata glucans (laminarin); animals with HSV injections fed U. pinnatifida fucoidans; animals with Staphylococcus aureus or Candida albicans injections fed S. cerevisiae glucans (scleroglucan); and animals with fecal solution injections fed an aqueous extract of A. subrufescens (A. blazei Murrill).

Additional controlled human and animal studies have shown anti-inflammatory and anti-allergy effects of some polysaccharide products. In an RCT of adults with seasonal allergic rhinitis, S. cerevisiae β-1,3;1-6 glucans decreased IL-4, IL-5 and percent eosinophils, and increased IL-12 in nasal fluid, while a placebo-controlled study of patients with recurrent aphthous stomatitis (canker sores) consuming β-1,3;1-6 glucans found increased lymphocyte proliferation and decreased Ulcer Severity Scores.

Animal models of inflammatory bowel disease have shown anti-inflammatory effects of Cladosiphon okamuranus Tokida fucoidans, Cyamopsis tetragonolobus galactomannans, Malus spp. pectins, and mixed polysaccharide supplements. Animals challenged with ovalbumin have demonstrated anti-inflammatory/allergy effects of A. subrufescens aqueous extracts, an aqueous extract of Ganoderma tsugae, and Pyrus pyrifolia pectins. Anti-inflammatory effects have also been seen in animals with cotton pellet implantations fed a Pholiota nameko heteroglycan (PNPS-1).

Trametes versicolor glucans have demonstrated anti-cancer effects in humans. In two RCTs and five controlled trials, PSK from T. versicolor mycelia increased survival of advanced stage gastric, colon and colorectal cancer patients with one study showing increased immune parameters (including blood NK cell activity, leukocyte cytotoxicity, proportion of helper cells and lymphocyte suppressor cells). An RCT of advanced stage lung cancer patients consuming PSP from T. versicolor fruit bodies found increased IgG and IgM antibodies and total leukocyte and neutrophil counts, along with a decrease in the number of patients withdrawing from the study due to disease progression. An RCT of ovarian or endometrial cancer patients consuming A. subrufescens glucans showed increased NK cell activity and fewer chemotherapy side effects.

In numerous animal models of cancer, a wide range of polysaccharides have shown anti-tumorogenic effects. Glucan products sourced from A. subrufescens demonstrating anti-cancer activities in animal models include an aqueous extract, an aqueous, acid-treated extract, and an aqueous extract with standardized levels of β-glucans. Anti-cancer effects have been reported following intake of aqueous extracts of G. lucidum; the powder and D fraction of G. frondosa; Hordeum vulgare β-glucans; Laminaria angustata powder; Lentinula edodes products (powders, SME, β-glucans, and lentinan); Pleurotus ostreatus powder, Saccharomyces cerevisiae particulate β-1,3;1,6 and β-1,3glucans; and a glucan from Sclerotinia sclerotiorum (SSG). A glucomannan from L. edodes (KS-2) improved survival of animals with cancer cell injections; apple and citrus pectins have exerted anti-cancer effects, including decreased tumor incidence. Finally, heteroglycans from Lycium barbarum (LBP3p), Lentinus lepidus (PG101) and A. subrufescens (ATOM) demonstrated a number of immune stimulating effects in animal cancer models. Interestingly, only one animal study has been performed using glucans from T. versicolor (PSP): animals with cancer cell implantations showed decreased tumor growth and vascular density.

Most polysaccharide products appear to be safe, based on NOAEL, acute and/or chronic toxicity testing in rodents (Table 6). As would be expected, powders, extracts and products that have not been fully characterized pose the most concerns. Other than for aloe vera gel, which was shown in a small human trial to increase the plasma bioavailability of vitamins C and E, the impact of polysaccharide intake on the absorption of nutrients and medications is not known. While one rat toxicity study raised concerns when guar gum comprised 15% of the daily diet, the product was safe in humans studies when 18-39.6 g/day was consumed for up to a year (Table 4). Product contamination may explain three case reports of hepatotoxicity and/or death following intake of an A. subrufescens aqueous extract. Seven animal studies reporting positive immunologic effects of A. subrufescens extracts in healthy animals or animals with cancers found no evidence of toxicity (Tables 1 and 2). In humans, six weeks of A. subrufescens glucans intake was safe for cancer patients, and four months of 3 g/day intake by 24 healthy adults and 24 adults with liver disease reported no evidence of toxicity (Table 4). Another case report associated liver toxicity with G. lucidum intake, but the elderly subject also took an unidentified product a month previous to her admission for testing. Three animal studies reported immunologic benefits and no adverse effects following intake of G. lucidum aqueous extracts; in one study intake was 5% of the diet for 5 months (Table 1). While adverse effects were also reported in a study in which 10 adults consumed 4 g/day L. edodes powder for 10 weeks, immunologic animal studies reported no ill effects of either L. edodes powder (5 studies, up to 5% of the diet up to nine months) or extract (7 studies, up to 40 days intake) (Tables 1 and 3). Finally, while intake of 319 mg/kg of an aqueous extract of P. ostreatus by mice for 1 month caused hemorrhages in multiple tissues, there was no reported toxicity when mice consumed the mushroom powder as 5% of their diet for nine months (Table 3). While ≥1 gram/day of T. versicolor glucan products were safely consumed by cancer patients for up to 10 years, the long-term effects of ingestion of the other polysaccharide products discussed in this review is also not known.

Discussion

The majority of studies that qualified for inclusion in this review employed models investigating immune stimulation; fewer explored anti-inflammatory effects. Animal studies reported immune system effects in the gut, spleen, bone marrow, liver, blood, thymus, lungs, and saliva; controlled human studies reported evidence of immune stimulation in the blood, anti-inflammatory effects in nasal lavage fluid and improved survival in cancer patients. The literature is highly heterogenous and is not sufficient to support broad structure/function generalizations. For the limited number of studies that investigated well-characterized, isolated products (primarily glucan products), effects can be unequivocally attributed to polysaccharides. Such associations are certainly more tenuous when considering product powders or products obtained by extraction methods designed to isolate polysaccharides, but without complete compositional analyses.

Dietary polysaccharides are known to impact gut microbial ecology, and advances in microbial ecology, immunology and metabolomics indicate that gut microbiota can impact host nutrition, immune modulation, resistance to pathogens, intestinal epithelial development and activity, and energy metabolism. Other than fucoidans, the polysaccharides discussed in this review appear to be at least partially degraded by bacterial enzymes in the human digestive tract (Table 7). Arabinogalactans, galactomannans, a glucan (laminarin), glucomannans, and mixed polysaccharide products (Ambrotose® products) have been shown to be metabolized by human colonic bacteria. Orally ingested fucoidans, glucans and mannans (or their fragments) have been detected in numerous tissues and organs throughout the body, (Carrington Laboratories, personal communication). We know of no study that has determined the specific identity of orally-ingested polysaccharide end products in animal or human tissues.

One can only speculate upon the mechanisms by which the polysaccharides discussed in this review influence immunologic function, particularly when one considers the exceedingly complex environment of the GI tract. It is possible that fragments of polysaccharides partially hydrolyzed by gut bacteria may either bind to gut epithelia and exert localized and/or systemic immune system effects, or be absorbed into the bloodstream, with the potential to exert systemic effects. Current studies investigating the link between the bioconversion of dietary polysaccharides, their bioavailability and their downstream effects on the host metabolism and physiology are utilizing metabolomic and metagenomic approaches that can detect and track diverse microbial metabolites from immunomodulatory polysaccharides. These and other innovative approaches in the field of colonic fermentation are providing novel insights into gut microbial-human mutualism, its impact on regulating human health and disease, and the importance of dietary modulation.

Additional RCTs of well-characterized products are needed to more completely understand the immunomodulatory effects and specific applications of oral polysaccharides. Such studies will need to better investigate the optimal timing and duration for polysaccharide ingestion. That is, should they be consumed continuously, before, at the time of, or after exposure to a pathogen or environmental insult? Only a few studies have actually investigated the impact of timing of polysaccharide intake to achieve optimal benefits. Daily feeding with some polysaccharides appears to result in tolerance (and diminished benefits); this has been demonstrated for some mushroom β-glucans. For those polysaccharides whose immunologic effects are dependent on their prebiotic activities, regular feeding would be presumed necessary.

Conclusions

The dietary polysaccharides included in this review have been shown to elicit diverse immunomodulatory effects in animal tissues, including the blood, GI tract, and spleen. In controlled human trials, polysaccharide intake stimulated the immune system in the blood of healthy adults, dampened the allergic response to a respiratory inflammatory agent, and improved survival in cancer patients. Additional RCTs of well-characterized products are needed to more completely understand the immunomodulatory effects and specific applications of oral polysaccharides

List of abbreviations

♀: female; ♂: male; Ab: antibody; AIDS: autoimmune deficiency syndrome; AOM: azoxymethane; BBN: N-butyl-N'-butanolnitrosamine; BLCL: Burkitt's Lymphoma Cell Line; BW: body weight; CBC: complete blood count; CD: cluster of differentiation; CFU: colony forming unit; ConA: concanavalin A; CXCR: CXC chemokine receptor; DMBA: 7,12-dimethylbenz(a)anthracene; DMH: N-N'-dimethylhydrazine; DMN: dimethylhydrazine; DSS: dextran sulfate sodium; EBV: Epstein-Barr virus; GALT: gut-associated lymphoid tissue; GI: gastrointestinal; H202: hydrogen peroxide; HSV: herpes simplex virus; ICR: imprinting control region; ID: intradermal; IEL: intraepithelial lymphocytes; IFN-λ: interferon gamma; IG: intragastric; IgA: immunoglobulin A; IgE: immunoglobulin E; IgG: immunoglobulin G; IgM: immunoglobulin M; IL: interleukin; IMC: invasive micropapillary carcinoma; IN: intranasally; IP: intraperitoneal; IV: intravenous; LPS: lipopolysaccharide; Mø: macrophage; mAb: monoclonal antibody; 3-MCA: methylcholanthrene; MLN: mesenteric lymph nodes; MM-46 carcinoma: mouse mammary carcinoma; MW: molecular weight; NK: natural killer; NOAEL: no observable adverse effect level; OVA: ovalbumin; PBL: peripheral blood leukocytes; PBMC: peripheral blood mononuclear cells; PHA: phytohaemagglutinin; PMA: phorbol 12-myristate 13-acetate; PML: polymorphonuclear lymphocyte; RCT: randomized, controlled trial; RNA: ribonucleic acid; SC: subcutaneous; SD rats: Sprague Dawley; TCR: T cell receptor; TLR: toll like receptor; TNF-α: tumor necrosis factor alpha; UC: ulcerative colitis; WT: wild type.

Competing interests

The authors are employees of the Research & Development Department at Mannatech, Incorporated, which sells two of the polysaccharide products (Ambrotose® powder and Advanced Ambrotose® powder) discussed in this review.

Authors' contributions

JER and EDN conducted literature searches and wrote the manuscript. RAS provided technical guidance. All authors read and approved the final manuscript.

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    Koetzner L Grover G Boulet J Jacoby H Plant-derived polysaccharide dietary supplements inhibits dextran sulfate sodium-induced colitis in the ratDig Dis Sci2010 5512781285

    Not in our library10.1007/s10620-009-0848-7

  53. 53.

    Lin JY Chen ML Lin BF Ganoderma tsugae in vivo modulates Th1/Th2 and macrophage responses in an allergic murine modelFood Chem Toxicol2006 4420252032

    Not in our library10.1016/j.fct.2006.07.002

  54. 54.

    Lee JC Pak SC Lee SH Na CS Lim SC Song CH Asian pear pectin administration during presensitization inhibits allergic response to ovalbumin in BALB/c miceJ Altern Complement Med2004 10527534

    Not in our library10.1089/1075553041323867

  55. 55.

    Li H Lu X Zhang S Lu M Liu H Anti-inflammatory activity of polysaccharide from Pholiota namekoBiochemistry (Mosc)2008 73669675

    Not in our library10.1134/s0006297908060060

  56. 56.

    Mitomi T Tsuchiya S Iijima N Aso K Suzuki K Nishiyama K Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa)Dis Colon Rectum1992 35123130

    Not in our library10.1007/bf02050666

  57. 57.

    Ito K Nakazato H Koike A Takagi H Saji S Baba S Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-upInt J Colorectal Dis2004 19157164

    Not in our library10.1007/s00384-003-0532-x

  58. 58.

    Ohwada S Ikeya T Yokomori T Kusaba T Roppongi T Takahashi T Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled studyBr J Cancer2004 9010031010

    Not in our library10.1038/sj.bjc.6601619

  59. 59.

    Nakazato H Koike A Saji S Ogawa N Sakamoto J Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric CancerLancet1994 34311221126

    Not in our library10.1016/s0140-6736(94)90233-x

  60. 60.

    Tsujitani S Kakeji Y Orita H Watanabe A Kohnoe S Baba H Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancerAnticancer Res1992 12645648

    Not in our library

  61. 61.

    Torisu M Hayashi Y Ishimitsu T Fujimura T Iwasaki K Katano M Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancerCancer Immunol Immunother1990 31261268

    Not in our library10.1007/bf01740932

  62. 62.

    Nio Y Tsubono M Tseng CC Morimoto H Kawabata K Masai Y Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancerBiotherapy1992 4117128

    Not in our library10.1007/bf02171756

  63. 63.

    Tsang KW Lam CL Yan C Mak JC Ooi GC Ho JC Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancerRespir Med2003 97618624

    Not in our library10.1053/rmed.2003.1490

  64. 64.

    Ahn WS Kim DJ Chae GT Lee JM Bae SM Sin JI 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 chemotherapyInt J Gynecol Cancer2004 14589594

    Not in our library10.1111/j.1048-891x.2004.14403.x

  65. 65.

    Murakawa K Fukunaga K Tanouchi M Hosokawa M Hossain Z Takahashi K Therapy of myeloma in vivo using marine phospholipid in combination with Agaricus blazei Murill as an immune respond activatorJ Oleo Sci2007 56179188

    Not in our library10.5650/jos.56.179

  66. 66.

    Kobayashi H Yoshida R Kanada Y Fukuda Y Yagyu T Inagaki K Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse modelJ Cancer Res Clin Oncol2005 131527538

    Not in our library10.1007/s00432-005-0672-1

  67. 67.

    Zhang Q-H Lin Z-B The antitumor activity of Ganoderma lucidum (Curt.:Fr.) P. Karst. (LingZhi) (Aphyllophoromycetidease) polysaccharides is related to tumor necrosis factor-alpha and interferon-gammaInt J Medicinal Mushrooms1999 207215

    Not in our library

  68. 68.

    Lu H Kyo E Uesaka T Katoh O Watanabe H A water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia suppresses azoxymethane-induction of colon cancers in male F344 ratsOncol Rep2003 10375379

    Not in our library

  69. 69.

    Lu H Kyo E Uesaka T Katoh O Watanabe H Prevention of development of N,N'-dimethylhydrazine-induced colon tumors by a water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia in male ICR miceInt J Mol Med2002 9113117

    Not in our library

  70. 70.

    Kurashige S Akuzawa Y Endo F Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamineImmunopharmacol Immunotoxicol1997 19175183

    Not in our library10.3109/08923979709007657

  71. 71.

    Hishida I Nanba H Kuroda H Antitumor activity exhibited by orally administered extract from fruit body of Grifola frondosa (maitake)Chem Pharm Bull (Tokyo)1988 3618191827

    Not in our library10.1248/cpb.36.1819

  72. 72.

    Nanba H Kubo K Effect of Maitake D-fraction on cancer preventionAnn N Y Acad Sci1997 833204207

    Not in our library10.1111/j.1749-6632.1997.tb48611.x

  73. 73.

    Hong F Yan J Baran JT Allendorf DJ Hansen RD Ostroff GR Mechanism by which orally administered (beta)-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor modelsJ Immunol2004 173797806

    Not in our library10.4049/jimmunol.173.2.797

  74. 74.

    Modak S Koehne G Vickers A O'Reilly RJ Cheung NK Rituximab therapy of lymphoma is enhanced by orally administered (1-->3),(1-->4)-D-beta-glucanLeuk Res2005 29679683

    Not in our library10.1016/j.leukres.2004.10.008

  75. 75.

    Cheung NK Modak S Vickers A Knuckles B Orally administered beta-glucans enhance anti-tumor effects of monoclonal antibodiesCancer Immunol Immunother2002 51557564

    Not in our library10.1007/s00262-002-0321-3

  76. 76.

    Cheung NK Modak S Oral (1-->3),(1-->4)-beta-D-glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastomaClin Cancer Res2002 812171223

    Not in our library

  77. 77.

    Teas J Harbison ML Gelman RS Dietary seaweed (Laminaria) and mammary carcinogenesis in ratsCancer Res1984 4427582761

    Not in our library

  78. 78.

    Nanba H Mori K Toyomasu T Kuroda H Antitumor action of shiitake (Lentinus edodes) fruit bodies orally administered to miceChem Pharm Bull (Tokyo)1987 3524532458

    Not in our library10.1248/cpb.35.2453

  79. 79.

    Sugui MM ves de Lima PL Delmanto RD da Eira AF Salvadori DM Ribeiro LR Antimutagenic effect of Lentinula edodes (BERK.) Pegler mushroom and possible variation among lineagesFood Chem Toxicol2003 41555560

    Not in our library10.1016/s0278-6915(02)00306-x

  80. 80.

    deVere White RW Hackman RM Soares SE Beckett LA Sun B Effects of a mushroom mycelium extract on the treatment of prostate cancerUrology2002 60640644

    Not in our library10.1016/s0090-4295(02)01856-3

  81. 81.

    Yap AT Ng M-L Immunopotentiating properties of lentinan (1-3)-b-D-glucan extracted from culinary-medicinal Shiitake mushroomInt J Medicinal Mushrooms2003 51939

    Not in our library

  82. 82.

    Ng ML Yap AT Inhibition of human colon carcinoma development by lentinan from shiitake mushrooms (Lentinus edodes)J Altern Complement Med2002 8581589

    Not in our library10.1089/107555302320825093

  83. 83.

    Suzuki I Sakurai T Hashimoto K Inhibition of experimental pulmonary metastasis of Lewis lung carcinoma by orally administered beta-glucan in miceChem Pharm Bull (Tokyo)1991 3916061608

    Not in our library10.1248/cpb.39.1606

  84. 84.

    Fujii T Maeda H Suzuki F Ishida N Isolation and characterization of a new antitumor polysaccharide, KS-2, extracted from culture mycelia of Lentinus edodesJ Antibiot (Tokyo)1978 3110791090

    Not in our library10.7164/antibiotics.31.1079

  85. 85.

    Ohkami H Tazawa K Yamashita I Effects of apple pectin on fecal bacterial enzymes in azoxymethane- induced rat colon carcinogenesisJpn J Cancer Res1995 86523529

    Not in our library10.1111/j.1349-7006.1995.tb02429.x

  86. 86.

    Watanabe K Reddy BS Weisburger JH Kritchevsky D Effect of dietary alfalfa, pectin, and wheat bran on azoxymethane- or methylnitrosourea-induced colon carcinogenesis in F344 ratsJ Natl Cancer Inst1979 63141145

    Not in our library

  87. 87.

    Hayashi A Gillen AC Lott JR Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c miceAltern Med Rev2000 5546552

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  88. 88.

    Pienta KJ Naik H Akhtar A Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectinJ Natl Cancer Inst1995 87348353

    Not in our library10.1093/jnci/87.5.348

  89. 89.

    Nangia-Makker P Hogan V Honjo Y Baccarini S Tait L Bresalier R Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectinJ Natl Cancer Inst2002 9418541862

    Not in our library10.1093/jnci/94.24.1854

  90. 90.

    Tazawa K Okami H Yamashita I Anticarcinogenic action of apple pectin on fecal enzyme activities and mucosal or portal prostaglandin E2 levels in experimental rat colon carcinogenesisJ Exp Clin Cancer Res1997 163338

    Not in our library

  91. 91.

    Gan L Hua ZS Liang Y Bi XH Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarumInt Immunopharmacol2004 4563569

    Not in our library10.1016/j.intimp.2004.01.023

  92. 92.

    Jin M Jeon H Jung HJ Kim B Shin SS Choi JJ Enhancement of repopulation and hematopoiesis of bone marrow cells in irradiated mice by oral administration of PG101, a water-soluble extract from Lentinus lepideusExp Biol Med (Maywood)2003 228759766

    Not in our library10.1177/153537020322800616

  93. 93.

    Ito H Shimura K Itoh H Kawade M Antitumor effects of a new polysaccharide-protein complex (ATOM) prepared from Agaricus blazei (Iwade strain 101) Himematsutake and its mechanisms in tumor-bearing miceAnticancer Res1997 17277284

    Not in our library

  94. 94.

    Ho JC Konerding MA Gaumann A Groth M Liu WK Fungal polysaccharopeptide inhibits tumor angiogenesis and tumor growth in miceLife Sci2004 7513431356

    Not in our library10.1016/j.lfs.2004.02.021

  95. 95.

    Vinson JA Al Kharrat H Andreoli L Effect of Aloe vera preparations on the human bioavailability of vitamins C and EPhytomedicine2005 12760765

    Not in our library10.1016/j.phymed.2003.12.013

  96. 96.

    Graham SL Arnold A Kasza L Ruffin GE Jackson RC Watkins TL Subchronic effects of guar gum in ratsFood Cosmet Toxicol1981 19287290

    Not in our library10.1016/0015-6264(81)90386-2

  97. 97.

    Mukai H Watanabe T Ando M Katsumata N An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patientsJpn J Clin Oncol2006 36808810

    Not in our library10.1093/jjco/hyl108

  98. 98.

    Yuen MF Ip P Ng WK Lai CL Hepatotoxicity due to a formulation of Ganoderma lucidum (lingzhi)J Hepatol2004 41686687

    Not in our library10.1016/j.jhep.2004.06.016

  99. 99.

    Levy AM Kita H Phillips SF Schkade PA Dyer PD Gleich GJ Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushroomsJ Allergy Clin Immunol1998 101613620

    Not in our library10.1016/s0091-6749(98)70168-x

  100. 100.

    Al Deen IH Twaij HA Al Badr AA Istarabadi TA Toxicologic and histopathologic studies of Pleurotus ostreatus mushroom in miceJ Ethnopharmacol1987 21297305

    Not in our library10.1016/0378-8741(87)90105-x

  101. 101.

    Flint HJ Duncan SH Scott KP Louis P Interactions and competition within the microbial community of the human colon: links between diet and healthEnviron Microbiol2007 911011111

    Not in our library10.1111/j.1462-2920.2007.01281.x

  102. 102.

    Macfarlane GT Steed H Macfarlane S Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebioticsJ Appl Microbiol2008 104305344

    Not in our library10.1111/j.1365-2672.2007.03520.x

  103. 103.

    Jacobs DM Gaudier E van DJ Vaughan EE Non-digestible food ingredients, colonic microbiota and the impact on gut health and immunity: a role for metabolomicsCurr Drug Metab2009 104154

    Not in our library10.2174/138920009787048383

  104. 104.

    Ishizuka S Tanaka S Xu H Hara H Fermentable dietary fiber potentiates the localization of immune cells in the rat large intestinal cryptsExp Biol Med (Maywood)2004 229876884

    Not in our library10.1177/153537020422900903

  105. 105.

    Garrett WS Gordon JI Glimcher LH Homeostasis and inflammation in the intestineCell2010 140859870

    Not in our library10.1016/j.cell.2010.01.023

  106. 106.

    Segain JP Raingeard de la BD Bourreille A Leray V Gervois N Rosales C Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's diseaseGut2000 47397403

    Not in our library10.1136/gut.47.3.397

  107. 107.

    Mazmanian SK Kasper DL The love-hate relationship between bacterial polysaccharides and the host immune systemNat Rev Immunol2006 6849858

    Not in our library10.1038/nri1956

  108. 108.

    Irhimeh MR Fitton JH Lowenthal RM Kongtawelert P A quantitative method to detect fucoidan in human plasma using a novel antibodyMethods Find Exp Clin Pharmacol2005 27705710

    Not in our library10.1358/mf.2005.27.10.948919

  109. 109.

    Sakurai MH Matsumoto T Kiyohara H Yamada H Detection and tissue distribution of anti-ulcer pectic polysaccharides from Bupleurum falcatum by polyclonal antibodyPlanta Med1996 62341346

    Not in our library10.1055/s-2006-957898

  110. 110.

    Arasaradnam RP Pharaoh MW Williams GJ Nwokolo CU Bardhan KD Kumar S Colonic fermentation--more than meets the noseMed Hypotheses2009 73753756

    Not in our library10.1016/j.mehy.2009.04.027

  111. 111.

    Possemiers S Grootaert C Vermeiren J Gross G Marzorati M Verstraete W The intestinal environment in health and disease - recent insights on the potential of intestinal bacteria to influence human healthCurr Pharm Des2009 1520512065

    Not in our library10.2174/138161209788489159

  112. 112.

    Liu J Gunn L Hansen R Yan J Yeast-derived beta-glucan in combination with anti-tumor monoclonal antibody therapy in cancerRecent Pat Anticancer Drug Discov2009 4101109

    Not in our library10.2174/157489209788452858

  113. 113.

    Tuohy KM Gougoulias C Shen Q Walton G Fava F Ramnani P Studying the human gut microbiota in the trans-omics era--focus on metagenomics and metabonomicsCurr Pharm Des2009 1514151427

    Not in our library10.2174/138161209788168182

  114. 114.

    Schiffrin EJ Morley JE Donnet-Hughes A Guigoz Y The inflammatory status of the elderly: The intestinal contributionMutat Res2010 6905056

    Not in our library10.1016/j.mrfmmm.2009.07.011

  115. 115.

    Leung MY Liu C Koon JC Fung KP Polysaccharide biological response modifiersImmunol Lett2006 105101114

    Not in our library10.1016/j.imlet.2006.01.009

  116. 116.

    Noda H Amano H Arashima K Hashimoto S Nisizawa K Antitumor activity of polysaccharides and lipids from marine algaeNippon Suisan Gakkaishi1989 512651271

    Not in our library

  117. 117.

    Wasser SP Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharidesAppl Microbiol Biotechnol2002 60258274

    Not in our library10.1007/s00253-002-1076-7

  118. 118.

    Firenzuoli F Gori L Lombardo G The medicinal mushroom Agaricus blazei Murrill: Review of literature and pharmaco-toxicological problemsEvid Based Complement Alternat Med2008 5315

    Not in our library10.1093/ecam/nem007

  119. 119.

    Luta G McAnalley B Aloe vera: chemical composition and methods used to determine its presence in commercial productsGlycoScience & Nutrition2005 6112

    Not in our library

  120. 120.

    Qiu Z Jones K Wylie M Jia Q Orndorff S Modified Aloe barbadensis polysaccharide with immunoregulatory activityPlanta Med2000 66152156

    Not in our library10.1055/s-2000-11125

  121. 121.

    Yagi A Nakamori J Yamada T Iwase H Tanaka T Kaneo Y In vivo metabolism of aloe mannanPlanta Med1999 65417420

    Not in our library10.1055/s-1999-14018

  122. 122.

    Pugh N Ross SA ElSohly MA Pasco DS Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activityJ Agric Food Chem2001 4910301034

    Not in our library10.1021/jf001036d

  123. 123.

    Final report on the safety assessment of Aloe andongensis extract, Aloe andongensis leaf juice, Aloe arborescens leaf extract, Aloe arborescens leaf juice, Aloe arborescens leaf protoplasts, Aloe barbadensis flower extract, Aloe barbadensis leaf, Aloe barbadensis leaf extract, Aloe barbadensis leaf juice, Aloe barbadensis leaf polysaccharides, Aloe barbadensis leaf water, Aloe ferox leaf extract, Aloe ferox leaf juice, and Aloe ferox leaf juice extractInt J Toxicol2007 26Suppl 2150

    Not in our library10.1080/10915810701351186

  124. 124.

    Akramiene D Kondrotas A Didziapetriene J Kevelaitis E Effects of beta-glucans on the immune systemMedicina (Kaunas)2007 43597606

    Not in our library

  125. 125.

    Kidd PM A new approach to metastatic cancer prevention: modified citrus pectin (MCP), a unique pectin that blocks cell surface lectinsAlt Med Rev1996 1410

    Not in our library

  126. 126.

    Nagaoka M Shibata H Kimura-Takagi I Hashimoto S Kimura K Makino T Structural study of fucoidan from Cladosiphon okamuranus TOKIDAGlycoconj J1999 161926

    Not in our library10.1023/a:1006945618657

  127. 127.

    Akaki J Matsui Y Kojima H Nakajima S Kamei K Tamesada M Structural analysis of monocyte activation constituents in cultured mycelia of Cordyceps sinensisFitoterapia2009 80182187

    Not in our library10.1016/j.fitote.2009.01.007

  128. 128.

    Whistler RL BeMiller JN Carbohydrate Chemistry for Food Scientists1999 2St. Paul, Minn.: American Association of Cereal Chemists, Inc

    Not in our library

  129. 129.

    Ohkuma T Otagiri K Ikekawa T Tanaka S Augmentation of antitumor activity by combined cryo-destruction of sarcoma 180 and protein-bound polysaccharide, EA6, isolated from Flammulina velutipes (Curt. ex Fr.) Sing. in ICR miceJ Pharmacobiodyn1982 5439444

    Not in our library10.1248/bpb1978.5.439

  130. 130.

    Wasser SP Coates PM, Blackman MR, Cragg GM, Levine M, Moss J, White JDReishi or Ling Zhi (Ganoderma lucidum)Encyclopedia of Dietary Supplements2005 New York, New York: Marcel Dekker603622

    Not in our library

  131. 131.

    Song G Xu A Chen H Wang X Component analysis on polysaccharides in exocarp of Ginkgo bilobaZhong Yao Cai1997 20461463

    Not in our library

  132. 132.

    Kubo K Nanba H Kuroda H Modification of cellullar immune responses in experimental autoimmune hepatitis in mice by maitake (Grifola frondosa)Mycoscience1998 39351360

    Not in our library10.1007/bf02460895

  133. 133.

    Berteau O Mulloy B Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharideGlycobiology2003 1329R40R

    Not in our library10.1093/glycob/cwg058

  134. 134.

    D'Adamo P Larch arabinogalactanJ Neuropath Med1990 63337

    Not in our library

  135. 135.

    Chihara G Maeda Y Hamuro J Sasaki T Fukuoka F Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) singNature1969 222687688

    Not in our library10.1038/222687a0

  136. 136.

    Chihara G Aoki T, Ichiro U, Eiro TThe antitumor polysaccharide Lentinan: an overviewManipulation of Host Defence Mechanisms1981 Excerpta Medica116

    Not in our library

  137. 137.

    Trnovec T Hrmova M Immunomodulatory polysaccharides: chemistry, disposition and metabolismBiopharm Drug Dispos1993 14187198

    Not in our library10.1002/bdd.2510140302

  138. 138.

    Jin M Jung HJ Choi JJ Jeon H Oh JH Kim B Activation of selective transcription factors and cytokines by water-soluble extract from Lentinus lepideusExperimental Biology and Medicine2003 228749758

    Not in our library10.1177/153537020322800615

  139. 139.

    Wasser SP Coates PM, Blackman MR, Cragg GM, Levine M, Moss J, White JDShiitake (Lentinus edodes)Encyclopedia of Dietary Supplements2005 New York, New York: Marcell Dekker653664

    Not in our library

  140. 140.

    Oshima Y Sato K Hikino H Isolation and hypoglycemic activity of quinquefolans A, B, and C, glycans of Panax quinquefolium rootsJ Nat Prod1987 50188190

    Not in our library10.1021/np50050a010

  141. 141.

    Zhu T Kim SH Chen CY A medicinal mushroom: Phellinus linteusCurr Med Chem2008 1513301335

    Not in our library10.2174/092986708784534929

  142. 142.

    Matsuba S Matsuno H Sakuma M Komatsu Y Phellinus linteus extract augments the immune response in mitomycin C-induced immunodeficient miceEvid Based Complement Alternat Med2008 58590

    Not in our library10.1093/ecam/nem001

  143. 143.

    Refaie FM Esmat AY Daba AS Taha SM Characterization of polysaccharopeptides from Pleurotus ostreatus mycelium: assessment of toxicity and immunomodulation in vivoMicologia Aplicada International2009 216775

    Not in our library

  144. 144.

    Babicek K Cechova I Simon RR Harwood M Cox DJ Toxicological assessment of a particulate yeast (1,3/1,6)-beta-D-glucan in ratsFood Chem Toxicol2007 4517191730

    Not in our library10.1016/j.fct.2007.03.013

  145. 145.

    Lehne G Haneberg B Gaustad P Johansen PW Preus H Abrahamsen TG Oral administration of a new soluble branched beta-1,3-D-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteersClin Exp Immunol2006 1436569

    Not in our library10.1111/j.1365-2249.2005.02962.x

  146. 146.

    Ng TB A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae)Gen Pharmacol1998 3014

    Not in our library10.1016/s0306-3623(97)00076-1

  147. 147.

    Tsukagoshi S Hashimoto Y Fujii G Kobayashi H Nomoto K Orita K Krestin (PSK)Cancer Treat Rev1984 11131155

    Not in our library10.1016/0305-7372(84)90005-7

  148. 148.

    Lee JB Hayashi K Hashimoto M Nakano T Hayashi T Novel antiviral fucoidan from sporophyll of Undaria pinnatifida (Mekabu)Chem Pharm Bull (Tokyo)2004 5210911094

    Not in our library10.1248/cpb.52.1091

  149. 149.

    Katsube T Yamasaki Y Iwamoto M Oka S Hyaluronidase-inhibiting polysaccharide isolated and purified from hot water extract of sporophyll of Undaria pinnatifidaFood Sci Technol2003 92529

    Not in our library10.3136/fstr.9.25

  150. 150.

    Koo JG Jo KS Do JR Woo SJ Isolation and purification of fucoidans from Laminara religiosa and Undaria pinnatifida in koreaJ Korean Fish Soc1995 28227236

    Not in our library

  151. 151.

    Tamboli S Arora S Bhatnagar U Vishwase G Singh M Reproductive and developmental toxicity evaluation of a purified Arabinogalactan-Protein (AGP) composition in Wistar ratsFitoterapia2010 81276283

    Not in our library10.1016/j.fitote.2009.10.001

  152. 152.

    Kim KJ Lee OH Lee HH Lee BY A 4-week repeated oral dose toxicity study of fucoidan from the Sporophyll of Undaria pinnatifida in Sprague-Dawley ratsToxicology2010 267154158

    Not in our library10.1016/j.tox.2009.11.007

  153. 153.

    Track NS Cawkwell ME Chin BC Chiu SS Haberer SA Honey CR Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effectsCan J Physiol Pharmacol1985 6311131121

    Not in our library10.1139/y85-183

  154. 154.

    Simons LA Gayst S Balasubramaniam S Ruys J Long-term treatment of hypercholesterolaemia with a new palatable formulation of guar gumAtherosclerosis1982 45101108

    Not in our library10.1016/0021-9150(82)90175-7

  155. 155.

    McIvor ME Cummings CC Van Duyn MA Leo TA Margolis S Behall KM Long-term effects of guar gum on blood lipidsAtherosclerosis1986 60713

    Not in our library10.1016/0021-9150(86)90081-x

  156. 156.

    Koujitani T Oishi H Kubo Y Maeda T Sekiya K Yasuba M Absence of detectable toxicity in rats fed partially hydrolyzed guarm gum (K-13) for 13 weeksInt J Toxicol1997 16611623

    Not in our library10.1080/109158197226928

  157. 157.

    Takahashi H Yang S Fujiki M Kim M Yamamoto T Greenberg N Toxocity studies of partially hydrolyzed guar gumJ Am Coll Toxicol1994 13273278

    Not in our library

  158. 158.

    Kuroiwa Y Nishikawa A Imazawa T Kanki K Kitamura Y Umemura T Lack of subchronic toxicity of an aqueous extract of Agaricus blazei Murrill in F344 ratsFood Chem Toxicol2005 4310471053

    Not in our library10.1016/j.fct.2005.02.007

  159. 159.

    The safety of extended consumption of freezing dryness Agaricus blazei (lwade strain 101) himematsutakeYakuri to Chiryo2006 34103117

    Not in our library

  160. 160.

    Tsuneo K Takahiko N Takashi F Masaaki O Michitaka S Ahikiro S Single dose toxicity study of powdered Grifola frondosa by oral administration in ratsPharmacometrics2003 653941

    Not in our library

  161. 161.

    Han YS Park SY Choi BK Choung SY Acute oral toxicity studies of extract of sanghwang mushroom (Phellinus linteus)J Appl Pharmacol2001 94650

    Not in our library

  162. 162.

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    Not in our library10.1021/jf00105a009

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    Salyers AA Vercellotti JR West SE Wilkins TD Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colonAppl Environ Microbiol1977 33319322

    Not in our library10.1128/aem.33.2.319-322.1977

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    Salyers AA Breakdown of polysaccharides by human intestinal bacteriaJ Environ Pathol Toxicol Oncol1985 5211231

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    Crociani F Alessandrini A Mucci MM Biavati B Degradation of complex carbohydrates by Bifidobacterium sppInt J Food Microbiol1994 24199210

    Not in our library10.1016/0168-1605(94)90119-8

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    Degnan BA Macfarlane GT Arabinogalactan utilization in continuous cultures of Bifidobacterium longum: Effect of co-culture with Bacteroides thetaiotaomicronAnaerobe1995 1103112

    Not in our library10.1006/anae.1995.1005

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    Imamura L Murai K Zhao C-J Takebe S Kobashi K Metabolism of arabinogalactan by rat and human intestinal microfloraBIFIDUS Flores, Fructus et Semina1992 61929

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    Michel C Lahaye M Bonnet C Mabeau S Barry JL In vitro fermentation by human faecal bacteria of total and purified dietary fibres from brown seaweedsBr J Nutr1996 75263280

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    Okubo T Ishihara N Takahashi H Fujisawa T Kim M Yamamoto T Effects of partially hydrolyzed guar gum intake on human intestinal microflora and its metabolismBiosci Biotech Biochem1994 5813641369

    Not in our library10.1271/bbb.58.1364

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    Deville C Gharbi M Dandrifosse G Peulen O Study on the effects of laminarin, a polysaccharide from seaweed, on gut characteristicsJ Sci Food Agric2007 8717171725

    Not in our library10.1002/jsfa.2901

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    Ikuzawa M Matsunaga K Nishiyama S Nakajima S Kobayashi Y Andoh T Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin)Int J Immunopharmacol1988 10415423

    Not in our library10.1016/0192-0561(88)90128-2

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    Yagi A Hamano S Tanaka T Kaneo Y Fujioka T Mihashi K Biodisposition of FITC-labeled aloemannan in micePlanta Med2001 67297300

    Not in our library10.1055/s-2001-14314

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    Marzorati M Verhelst A Luta G Sinnott R Verstraete W Van de Wiele T In vitro modulation of the human gastrointestinal microbial community by plant-derived polysaccharide-rich dietary supplementsInt J Food Microbiol2010 139168176

    Not in our library10.1016/j.ijfoodmicro.2010.02.030

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    Salyers AA West SE Vercellotti JR Wilkins TD Fermentation of mucins and plant polysaccharides by anaerobic bacteria from the human colonAppl Environ Microbiol1977 34529533

    Not in our library10.1128/aem.34.5.529-533.1977

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