Polysaccharides: Therapeutic Constituents in Medicinal Mushrooms, Part 1

Polysaccharides are a major component of the fungal cell wall and possibly the most potent and abundant therapeutic constituent in mushroom medicine. They are well-touted for their immune regulatory activity, but they play a role in many other important physiologic processes including blood sugar regulation, inflammation modulation, antioxidant activity, mood support, and modulation of the intestinal microbiome and the greater intestinal environment.

Biologic Response Modifiers

The fungal cell wall is composed of many layers – mannoproteins, ß- (1,6)-glucan and ß-(1,3)-glucan, and chitin. Humans do not make chitinase, and cannot utilize chitin for anything other than non-digestible fiber. Chitin can, however, be broken down by different processing techniques, including heat, allowing the mannan and beta-glucan layers to be utilized as medicine. From an immunological perspective, these layers are considered pathogen-associated molecular patterns (PAMPs), and bind to pathogen recognition receptors (PRRs) on cells in the innate immune system - macrophages, granulocytes, dendritic cells and natural killer cells. The majority of binding occurs in the gut-associated lymphoid tissue (GALT), where Peyer’s patches contain cells of the innate immune system. Specific receptors that bind these ß-glucans include Dectin-1 and TLR-2 (1). Binding has a hormetic effect, creating a stress response in our immune system, stimulating the release of cytokines with anti-inflammatory, pro-inflammatory, and other immune-modulating actions. These cytokines stimulate an increase in natural killer cells and cytotoxic T cells, generating a stress signal that leads to a more responsive immune system.
Beta glucan structure
ß- (1,6)-glucan and ß-(1,3)-glucan

Blood sugar-regulation

ß-glucan polysaccharides from mushrooms inhibit the enzyme alpha-glucosidase, which is essential for carbohydrate metabolism and for generating a rise in blood sugar following a meal. They have also been shown to decrease gastric emptying, slowing the absorption of glucose, and preventing hyperglycemic episodes. Finally, polysaccharides demonstrate the ability to upregulate GLUT 4, an insulin-response glucose transporter, while down-regulating NF-κB, a nuclear transcription factor that regulates inflammation (2,3).


ß-glucan polysaccharides increase the activity of hepatic oxidative enzymes such as catalase, glutathione peroxidase, and superoxide dismutase, increasing levels of glutathione and decreasing malondialdehyde levels (a marker of lipid peroxidation). Generally, these compounds support our innate antioxidant systems, relieving oxidative stress, and reducing free radical damage (4).


The oligosaccharides and polysaccharides contained in mushrooms are consumed by Bifidobacterium and Lactobacilli, two important bacterial phyla in a healthy microbiome (5,6). Polysaccharides also promote production of important postbiotics like butyric acid, a short chain fatty acid, which provides colon cells with about 70% of their total energy needs (7).


Polysaccharides play a role in creating a healthy intestinal ecosystem through potentiating the growth of healthy bacteria, archaea and fungi while also supporting a more resilient gastrointestinal terrain. Healthy gut flora and intestinal mucosa are associated with better mood. Signals from the GI tract can independently relay information to the central nervous system, and the maintenance of a healthy GI tract supports a balanced central nervous system. There are a number of studies that have demonstrated increased probiotic intake associated with increased mood and diminished anxiety (8). Specifically, probiotic supplementation with Lactobacillus helveticus and Bifidobacterium longum showed less self-reported negative mood and decreased urinary cortisol. A similar effect was also observed in healthy participants who consumed a mixture of Bifidobacterium bifidum and Bifidobacterium lactis, and Lactobacillus acidophilus, Brevibacillus brevis, Brevibacterium casei, Bifidobacterium salivarius, and Lactococcus lactis (9,10).


Raw mushroom preparations (including products labeled “mushroom powder”) have not undergone sufficient processing to break down the chitin in the cell wall, leaving ß-glucans unavailable for absorption; extractions employ heat, water, and alcohol to free ß-glucans, improving their absorption and activity. While mixing mushrooms with coffee, tea, or chocolate is increasingly popular, the tannins in these foods bind the fungal polysaccharides, diminishing bioavailability (11). For best results, take polysaccharide-rich mushroom preparation on an empty stomach, away from food.

DIY Extraction of Polysaccharides

Polysaccharides are water soluble and high molecular weight (heavy molecules that don’t evaporate)
  1. Boil chopped (fresh or dried) mushrooms in water for about 2 hours
  2. Use this polysaccharide-rich broth as a base for cooking rice, stews, soups and teas


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  2. Vitak T, Yurkiv B, Wasser S, Nevo E, Sybirna N. Effect of medicinal mushrooms on blood cells under conditions of diabetes mellitus. 2017;8(5):187-201. doi:10.4239/wjd.v8.i5.187.
  3. Chen Y, Liu Y, Rahman M, Yan X, Yang C. Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1 / PI3K-JNK signaling pathways. Carbohydr Polym. 2018;198(15):452-461. doi:10.1016/j.carbpol.2018.06.077.
  4. Wang H, Liu YM, Qi ZM, et al. An Overview on Natural Polysaccharides with Antioxidant Properties. 2015;(February). doi:10.2174/0929867311320230006.
  5. Yu Z, Liu B, Mukherjee P, Newburg DS. Trametes versicolor Extract Modifies Human Fecal Microbiota Composition In vitro. 2013:107-112. doi:10.1007/s11130-013-0342-4.
  6. Palacios S, Losa F, Dexeus D, Cortés J. Beneficial effects of a Coriolus versicolor - based vaginal gel on cervical epithelization , vaginal microbiota and vaginal health : a pilot study in asymptomatic women. 2017:4-9. doi:10.1186/s12905-017-0374-2.
  7. Verhoeven J, Keller D, Verbruggen S, Abboud KY, Venema K. A blend of 3 mushrooms dose-dependently increases butyrate production by the gut microbiota. Benef Microbes. 2021 Nov 16;12(6):601-612. doi: 10.3920/BM2021.0015. Epub 2021 Sep 30. PMID: 34590532.
  8. Messaoudi M, Violle N, Bisson J-F, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2011;2:256– 261.
  9. Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun 2015;48:258–264.
  10. Allen AP, HutchW, Borre YE, et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry 2016;6:e939.
  11. Li R, Zeng Z, Fu G, Wan Y, Liu C, McClements DJ. Formation and characterization of tannic acid/beta-glucan complexes: Influence of pH, ionic strength, and temperature. Food Res Int. 2019;120:748-755. doi:10.1016/j.foodres.2018.11.034