Fungi Parts and Medicinal Quality – Not Just Semantics

All mushrooms are fungi, but not all fungi are mushrooms

A mushroom is the macroscopic, above-ground portion of the fungal organism. The mycelium is the root portion of the fungi that is rarely seen; it is usually found within a rotting tree trunk, or in a dense underground network. Similar to the way that humans digest and absorb nutrients, mycelia excrete enzymes that break down the waste of the forest, and use this energy to form a mushroom, or a fruit body. When the mushroom has fully matured, seed-like spores are released and wind and insects carry them to their next place of inoculation. The spores, mycelium, and mushroom are all vital aspects of the fungal organism and are, more specifically, different life stages of the fungi. A spore is not a mushroom, a mushroom is not mycelium, and mycelium is most definitely not a mushroom.

Until recently, mycelium was not used medicinally. The energy and time it would take to dig up mycelium from the earth, or separate it from a rotting tree trunk, would far outweigh the medicinal benefit from the small amount of mycelium collected. Traditionally humans, being the innately lazy animals that we are, preferred to spend a few minutes to collect the colorful mushrooms and use them as medicine rather than spend hours digging up and separating out mycelium from rotting flora. If all mushroom products were made from wild harvested fruiting bodies, there would likely be no market for mycelium. Unfortunately, this would not be sustainable, so many companies have developed sterile laboratories where they can cultivate mycelium grown on grain substrate. The same issue returns, however – the cost of the time it would take to separate all the mycelium from the grain is not economically viable. So, the mycelium is not separated from the substrate it is grown on, and the entire block of myceliated grain is dried, powdered, bottled up, and advertised as a mushroom supplement.

Mycelium as a medicine

Mycelium contains many similar medicinal compounds to mushrooms, but often to a lesser degree, with the exception of some polysaccharides. While the majority of research has focused on mushrooms, there is still a fair amount of research touting the health benefits and active compounds present in mycelium. However, these trials utilize mycelium that is grown in a liquid fermentation broth rather than the myceliated-grain that is found in many health food store and apothecary shelves. When mycelium is grown in a broth, the liquid can be strained off and pure mycelium can be processed. However, as mentioned earlier, when mycelium is grown on grain, it is not filtered out or separated and many products can contain up to 60% grain. Pure mycelium from a number of different fungal species absolutely has medicinal value, but that value is heavily diluted when 250mg of your 500mg capsule is oat or sorghum substrate.

A Comparison of Constituents

As mycelium matures into a mushroom, the organism’s energy is focused on reproduction, and there is a vast increase in production of many compounds that happen to be beneficial to humans. One study (1) compared the amount of GABA, lovastatin and ergothioneine in mycelium with that found in mushrooms. GABA, a calming neurotransmitter, was found in equal amounts in both mushroom and mycelium. Lovastatin, a compound that helps to support healthy cholesterol levels, was found to be especially high in the fruiting body of oyster mushroom in comparison to mycelium. Finally, ergothioneine, an extraordinary antioxidant, was found both in oyster mycelium and mushroom, but to a much larger extent in the mushroom.

Another study (2) compared the antioxidant activity of reishi mushroom, spores and mycelium. Reishi mushroom yielded the highest antioxidant activity via phenolic compounds in the extracts. The mycelium contained the highest total level of polysaccharides and single sugar molecules, but the free-radical scavenging properties seemed to be correlated most with the phenolic compounds found in the fruiting body. The chemical makeup of reishi mycelium, fruiting body, and spores powder was explored by another team of researchers (3). They observed the presence of polysaccharides, nucleosides, peptides, triterpenoids and alkaloids present in different fungal life stages. Triterpenoids, especially ganoderic acids, were found in all life stages of the fungal organism, but were by far most abundant in the fruit body, and least abundant in the mycelium. Triterpenoids support a healthy inflammatory response, modulate the immune system, support liver pathways and support healthy cholesterol levels. Their results demonstrated that the polysaccharide content in all parts of reishi were  almost the same, with the most upregulated in the fermentation broth.

Polysaccharides, alpha glucans and beta glucans

Polysaccharides are sugar molecules attached by different bonds, some alpha and some beta. The kind of bond determines the physiological activity of the ingested polysaccharide. When exploring the medicinal value of fungi, the beta bond, or β-glucan, is preferred. Many grains contain starch, or alpha-glucans, which can sometimes be confused in the total polysaccharide content of a mushroom supplement. If 60% of a myceliated grain powder contains a high amount of polysaccharides, it is important to differentiate between those derived from the mycelium and those derived from the grain.

β-glucans are the most comprehensively studied constituents in medicinal fungi. Scientists have determined exactly which receptors they bind to, how they bind, where they bind, and the physiological activities that take place afterwards. β-glucans help to support many body systems – a healthy immune system, blood sugar levels and microbiome, to name a few. 

The β-glucan content of shiitake fruit body and mycelium was compared by Bak in 2014 (4). Researchers presented a quantitative analysis of β-glucan levels in three sections of the mushroom: stipe (stalk), pileus (cap) and mycelium. The highest β-glucan content was observed in the stipe, or stalk, section of the shiitake fruiting bodies. β-glucan content seems to depend on the degree of fruiting body maturity – the highest level of these compounds seems to be present immediately prior to the period in which the spores begin to ripen (5). Based on this information, mushrooms are likely the best source for β-glucans.


While mycelium is not devoid of medicinal value, most mycelium available for purchase is diluted by grain substrate, and the medicinal value is diluted as well. For this reason, pure fruit bodies that have been extracted and dried or extracted into a quality liquid extract are preferred when using fungi as a medicine. While the ideal product would likely contain pure mycelium mixed with fruiting body, this has yet to exist on the market without grain substrate involved.

Work Cited:

  1. Lo, Y.-C., Lin, S.-Y., Ulziijargal, E., Chen, S.-Y., Chien, R.-C., Tzou, Y.-J., & Mau, J.-L. (2012). Comparative Study of Contents of Several Bioactive Components in Fruiting Bodies and Mycelia of Culinary-Medicinal Mushrooms. International Journal of Medicinal Mushrooms. International Journal of medicinal mushrooms, Volume 14,2021, issue 4
  2. Sandrina A. Heleno, Lillian Barros, Anabela Martins, Maria João R.P. Queiroz, Celestino Santos-Buelga, Isabel C.F.R. Ferreira, Fruiting body, spores and in vitro produced mycelium of Ganoderma lucidum from Northeast Portugal: A comparative study of the antioxidant potential of phenolic and polysaccharidic extracts, Food Research International, Volume 46, Issue 1, 2012, Pages 135-140,ISSN 0963-9969
  3. Chunliang Xie, Shaowei Yan, Zhoumei Zhang, Wenbing Gong, Zuohua Zhu, Yingjun Zhou, Li Yan, Zhenxiu Hu, Lianzhong Ai, Yuande Peng, Mapping the metabolic signatures of fermentation broth, mycelium, fruiting body and spores powder from Ganoderma lucidum by untargeted metabolomics, LWT, Volume 129, 2020, 109494, ISSN 0023-6438,
  4. Bak WC, Park JH, Park YA, Ka KH. Determination of Glucan Contents in the Fruiting Bodies and Mycelia of Lentinula edodes Cultivars. Mycobiology. 2014 Sep;42(3):301-4. doi: 10.5941/MYCO.2014.42.3.301. Epub 2014 Sep 30. PMID: 25346611; PMCID: PMC4206800.
  5. Rop O, Mlcek J, Jurikova T. Beta-glucans in higher fungi and their health effects. Nutr Rev. 2009;67(11):624-631. doi:10.1111/j.1753-4887.2009.00230.x

Are you absorbing your mushroom supplements?

Mushroom supplements come in many varieties, and it is important to consider not only the dose form but also how they are prepared for consumption, and how they are consumed. There are a few major factors that impact optimal bioavailability of active constituents.

Let’s begin by addressing two active constituents that are responsible for the therapeutic benefits of mushrooms: polysaccharides and triterpenes.

Active constituents


Polysaccharide (1-3, 1-6) ß-glucans are ubiquitous in medicinal mushrooms. ß-glucans are an integral aspect of the mushroom cell wall, and are structurally bound within a substance called chitin, best known as the main structural component in crustacean shells. When a mushroom goes through any kind of heating process, medicinal ß-glucans are unbound from chitin, and become bioavailable.

Vega, K., & Kalkum, M. (2012). Chitin, Chitinase Responses, and Invasive Fungal Infections. International Journal of Microbiology, 2012, 920459.

After ingestion, ß-glucans survive stomach acid, bile, and other digestive secretions essentially unchanged. The major physiological effects induced by ß-glucans occur within the small intestine, where they bind to specific receptors on immune cells present within the gut associated lymphoid tissue (GALT).

Following ß-glucan binding to the receptors, a number of different immune regulatory processes take place, including indirect immune effects via modulation of the  intestinal microbiota. ß-glucans can act as substrate for beneficial flora present in the small intestine, helping to outcompete pathogenic intestinal flora. Beneficial bacteria that consume ß-glucans excrete the short chain fatty acid butyrate (1), which is also important for immune regulation and intestinal health.


The triterpenes present in medicinal mushrooms are most commonly lanostane triterpene glycosides, or lanostenoids. While ß-glucans stimulate immunoregulatory pathways via the GALT and intestinal microbiota, triterpene glycosides have exhibited direct antineoplastic and anti-viral activity both in vitro and in vivo

Ganoderic acid

Unfortunately, triterpenes are not well absorbed following oral consumption, and we have yet to see any mushroom supplement companies recommending injection of their products (though it goes without saying: do not inject your mushroom extracts!). Around 10% of the triterpenes present in mushroom extracts is bioavailable (2), and this relatively poor bioavailability may be due to first pass metabolism through the liver and conversion of triterpene glycosides to metabolites via intestinal bacteria. Furthermore, consuming food with mushroom extracts delays and inhibits absorption of these medicinal compounds.

Factors that interfere with absorption of Beta-glucans and triterpenes

Eating mushrooms raw 

Some supplement labels may list their mushroom ingredients as “mushroom powder”. It is safe to assume that unless the product specifically states that it contains powdered extract, the mushrooms present have been dehydrated and powdered. Typical dehydration methods do not use enough heat to break down the chitin in the cell wall, leaving the ß-glucan fraction unavailable for its immune-modulating and prebiotic effects.

Given the undigested nature of dehydrated mushroom powders, consuming powdered mushrooms is largely equivalent to consuming very expensive fiber. Choose products that state “powdered mushroom extracts” or “mushroom extracts” on their labels to ensure they contain appropriately processed ß-glucans.

Blending mushrooms with coffee, tea, or chocolate

Mushroom extracts blended with tannin-rich foods like coffee, tea and chocolate will likely not be absorbed as well as mushroom extract taken alone. When blended or emulsified, polysaccharides and tannins can bind strongly to each other, and these bonds can survive the stomach without breaking. When this tannin-ß-glucan complex reaches the small intestine, the ß-glucans will not be recognized by immune cell receptors essential for promoting immunoregulatory processes. (3)

Taking mushroom extracts with food

Consuming mushroom extracts with food can significantly alter the speed and extent of absorption of triterpene glycosides. (1). For this reason, it is not recommended to use mushroom extract powders mixed into foods. For optimal absorption of the already low bioavailable triterpenes, take triterpene-containing mushroom supplements on an empty stomach.

N.B. It has been speculated that consuming vitamin C with mushroom extracts may enhance absorption but unfortunately this seems to be a myth. (4).


For the best absorption and bioavailability, take your mushrooms extracted, plain and simple, with water, and nothing else.

Work Cited:

  1. 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;12(6):601-612. doi:10.3920/BM2021.0015
  2. Teekachunhatean, S., Sadja, S., Ampasavate, C., Chiranthanut, N., Rojanasthien, N., & Sangdee, C. (2012). Pharmacokinetics of Ganoderic Acids A and F after Oral Administration of Ling Zhi Preparation in Healthy Male Volunteers. Evidence-Based Complementary and Alternative Medicine, 2012, 780892.
  3. 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
  4. Tawasri P, Ampasavate C, Tharatha S, Chiranthanut N, Teekachunhatean S. Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study. Biomed Res Int. 2016;2016:2819862. doi:10.1155/2016/2819862

coffee, tea, chocolate and mushrooms: A mismatch of mediums?

The flavor of mushrooms is not for everyone, and many ‘functional’ food companies are well aware of this. Some of these companies formulate mushrooms in teas, chocolates and coffee so that their consumers can benefit from the mushrooms without having to deal with their ‘mushroomy’ flavor. In fact, many of them claim that mushrooms in these formulations even have enhanced medicinal properties. Although I am all for getting more mushroom medicine into more people, I think it is important for people to look into the interactions between different biomolecules before making claims about the medicinal quality of their products.

The interactions between various polyphenols (like tannins), and polysaccharides, are of particular interest. Polyphenols are found in varying degrees in coffee, tea and chocolate, and are also found in many other herbs and foods, but for the purposes of this article I will keep our discussion specific to foods that mushrooms are often formulated with (1, 2).

The polyphenols present in coffee, tea and chocolate have many health benefits, including anti-oxidant, anti-inflammatory and anti-microbial activity (3). The issue is not the medicinal qualities of polyphenols, but that when blended with mushroom extracts, they create bonds with polysaccharides (4, 5).

Abstract Image
Polysaccharides (left) Polyphenols (center) Polysaccharide-Polyphenol Complex (right)
J. Agric. Food Chem. 2013, 61, 19, 4533–4538
Publication Date:April 26, 2013

Immune-modulating polysaccharides are the most well-researched component of mushroom medicine. In order for polysaccharides to exert an immune-modulating effect, they need to bind to specific receptors on immune cells within the gut-associated-lymphoid-tissue (GALT) (6). If the polysaccharides are bound to polyphenols, they cannot bind to these receptors, and the immune-modulating benefits that these products are touted for become obsolete.

Important caveats:

The bonds between polysaccharides and polyphenols are hydrogen bonds, and are easily affected by temperature and pH:

Temperature: Bonds become less stable as temperature increases from 68F to 104F. You may want to blend your mushroom extracts with your coffee, chocolate and tea while the temperature is high. If the temperature is too low, the bonds will remain strong, even in stomach acid.

pH: Bonds become less stable as pH increases from 2 to 9. Stronger bonds seem to be made under more acidic conditions. The pH of stomach acid is around 1.5 to 3.5. Therefore, stomach acid will NOT break these bonds, and they will remain intact as the complexes enter the small intestine. Polysaccharides contained in these complexes will NOT be available to bind immune receptors in the GALT, and their immune-modulating properties will be nullified.

But all is not lost!

Polyphenols as well as polysaccharides exert many benefits on gut microbiota, and a healthy gut microbiome is imperative to strong immunity (7, 8, 9). I suspect that if these polyphenol-polysaccharide complexes make their way to the colon, their beneficial impacts on the microbiome do enhance the immune system, but through a different pathway than in the small intestine.

Work Cited

  1. Savolainen H. Tannin content of tea and coffee. J Appl Toxicol. 1992 Jun;12(3):191-2. doi: 10.1002/jat.2550120307. PMID: 1629514.
  2. Jalil AM, Ismail A. Polyphenols in cocoa and cocoa products: is there a link between antioxidant properties and health?. Molecules. 2008;13(9):2190-2219. Published 2008 Sep 16. doi:10.3390/molecules13092190
  3. Chung KT, Wong TY, Wei CI, Huang YW, Lin Y. Tannins and human health: a review. Crit Rev Food Sci Nutr. 1998 Aug;38(6):421-64. doi: 10.1080/10408699891274273. PMID: 9759559.
  4. Wang Y, Liu J, Chen F, Zhao G. Effects of molecular structure of polyphenols on their noncovalent interactions with oat β-glucan. J Agric Food Chem. 2013 May 15;61(19):4533-8. doi: 10.1021/jf400471u. Epub 2013 May 6. PMID: 23647238.
  5. Li, R., Zeng, Z., Fu, G., Wan, Y., Liu, C., & McClements, D. J. (2019). Formation and characterization of tannic acid/beta-glucan complexes: Influence of pH, ionic strength, and temperature. Food Research International120, 748–755.
  6. Camilli, G., Tabouret, G., & Quintin, J. (2018). The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System. Frontiers in Immunology9, 673.
  7. Kumar Singh A, Cabral C, Kumar R, et al. Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency. Nutrients. 2019;11(9):2216. Published 2019 Sep 13. doi:10.3390/nu11092216Ho Do M, Seo YS, Park HY. Polysaccharides: bowel health and gut microbiota. Crit Rev Food Sci Nutr. 2021;61(7):1212-1224. doi: 10.1080/10408398.2020.1755949. Epub 2020 Apr 22. PMID: 32319786.Savolainen H. Tannin content of tea and coffee. J Appl Toxicol. 1992 Jun;12(3):191-2. doi: 10.1002/jat.2550120307. PMID: 1629514.
  8. Ho Do M, Seo YS, Park HY. Polysaccharides: bowel health and gut microbiota. Crit Rev Food Sci Nutr. 2021;61(7):1212-1224. doi: 10.1080/10408398.2020.1755949. Epub 2020 Apr 22. PMID: 32319786.
  9. Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res 30, 492–506 (2020).

Medicinal Mushrooms – Going Viral

Mushrooms have been used as both food and medicine since antiquity. One of my favorite poems, discovered in an ancient Egyptian temple, illustrates this history: “Without leaves, without buds, without flowers, yet from fruit; as food, as tonic, as medicine: the entire creation is precious.” At a time when viral epidemics are inevitable and the current COVID-19 pandemic has presented in most of the world, antiviral therapies are possibly being investigated now more than ever before.  This paper explores the use of medicinal mushrooms as antivirals in in vivo (human and animal) and in vitro (petri dish) experiments and how these experiments may inform us on the utilization of these fungi as antiviral therapies.

Medicinal mushrooms are known as biological response modifiers. This physiologic modification is largely a result of the interaction of various mushroom constituents, primarily polysaccharides, with the immune system. Therefore, to understand the role that medicinal mushrooms play as antiviral agents, it is imperative to understand the happenings of the immune system in response to a viral pathogen and the interplay between mushrooms, their constituents, and this system. Unlike pharmaceutical antivirals, the actions of medicinal mushrooms are not straightforward, and there is no absolute rule that mushrooms stimulate or depress immunity. Mushrooms contain many constituents and are dynamic in their interplay with the human body.

Overview of anti-viral immunity 

The initial immune response to a new pathogen is facilitated by the innate immune system (innate meaning inborn or natural). This is our first response to non-self organisms, and requires no other stimulation than the pathogen itself. It is the response that is ready to go at all moments in the day and persistently protects the human body from infection. It is easy to imagine that an altered or defective innate immune response can have a detrimental effect on the ability to fight disease.

The innate immune response to a virus is multidimensional. There is a massive amount of cell-to-cell communication and different chemicals (called cytokines) are released to make this communication possible. Once an epithelial cell (cells that make up the surface of different body tissues like skin, lungs, etc) is infected with a virus, Type 1 Interferon (Interferon-α, a cytokine) is released and has three major functions: to induce resistance to viral replication in all cells, to increase expression of ligands for receptors on natural killer (NK) cells, and to activate NK cells to kill virus infected cells. NK cells are lymphocytes (a small white blood cell that is found primarily in the lymphatic system) that defend against viral infections and tumor cells via cytokine stimulation and direct killing of infected cells. NK cells provide such a vital role in antiviral immunity that people deficient in NK cells suffer from persistent viral infections. These functions of NK cells are important in regards to understanding medicinal mushrooms and their role in antiviral immunity.

Imagine the immune response to a newly inhaled viral particle. This virus enters the healthy person’s lungs and invades the lung epithelium. Once an epithelial cell is infected, it releases Type 1 Interferon, which turns circulating NK cells into cytotoxic effector NK cells (NK cells primed to seek out and kill virally infected cells). The cytotoxic effector NK cells promptly start the process of seeking out infected cells and the innate immune response commences. At the same time, there are resident macrophages in the respiratory epithelium and throughout the body. These macrophages (“big eaters”), are also major players in the innate immune response. Their role is to consume these virus particles and produce chemicals (cytokines and chemokines) that attract and engage more NK cells and also T cells. An important cytokine engaged in this process is interleukin-12 (IL-12), which stimulates NK cells to not become cytotoxic, but rather effector NK cells. Unlike cytotoxic effector NK cells, these effector NK cells stimulate an inflammatory response via Type 2 Interferon (IFN-γ), at the site of infection. This inflammatory cascade consists of IL-1, IL-6, TNF-α, and IL-12, and is essential for viral eradication. It is only when this response is out of control that it becomes problematic and detrimental to the host.1,2,3,4 If this initial response is not primed for viral combat, viral particles continue to proliferate and infect more healthy cells. It is in this phase that medicinal mushrooms can have a great impact to prevent viral infections from taking over the host.

Cytokine Source Role
IFN-α Virus infected epithelium Circulating NK cells –>Cytotoxic effector NK cells
IL-12 Macrophage post virus consumption NK cells –> effector NK cells
IFN- γ Effector NK cells Macrophages –> inflammatory cytokines (TNF-α, IL-2, IL-1, IL-6)
TNF- α Macrophages Induces blood vessels more permeable, enabling effector cells to enter infected tissue
IL-1 Macrophages Induces blood vessels more permeable, enabling effector cells to enter infected tissue
IL-6 Macrophages Induces fat and muscle cells to metabolize, make heat and raise temperature of infected tissue
IL-12 Macrophages Recruits and activates NK cells –> secrete more cytokines that strengthen macrophage response to infection
IL-10 Toxic substances secreted by macrophages–> TH2 Suppress macrophage activation
IL-4 Toxic substances secreted by macrophages–> TH2 Suppress macrophage activation


COVID-19 is an excellent example of these two main immune responses.5 The first stage of infection is the less severe incubation phase. The previously mentioned immune response is imperative to eliminate the virus and keep disease from progressing to later, more severe stages. It is in the incubation stage that immune-stimulating therapies are most indicated. In more severe stages, the protective immune response is impaired and the virus will spread and destroy healthy cells. Because damaged cells induce inflammation, immune stimulation is less indicated and it is more favorable to treat with anti-inflammatory therapies. It is at this stage of disease, characterized by severe lung inflammation, that life-threatening respiratory disorders occur and the feared cytokine storm is initiated. The cytokine storm is an influx of inflammatory cytokines. It is an overdramatic immune response that is harmful to the host and can often lead to acute respiratory distress syndrome. The inflammatory cytokines that are so important for stage one of the disease ( IL-1, IL6, TNF-α, and IL-12) are now abundant, destructive and out of control.6,7

The two phase division of the immune response is very important . The first immune response is protective and a response that can be altered through diet and lifestyle: our base response when initially combating infection. As mentioned previously, this is the phase where medicinal mushrooms are most indicated. They are primers of the first response to viral particles.


Antiviral immunity in healthy adults

The most informative studies exploring the interaction of medicinal mushrooms and the immune response are done on healthy human adults. In these studies it is ideal to see cytokine and NK cell levels before and after mushroom intake in healthy people to get a good idea of how exactly the mushrooms are priming our innate response. There are not many studies of this kind, but there are a few.

Healthy Korean men who took 1.5g/day of powdered extract of Cordyceps militaris brown rice culture for four weeks had their blood analyzed before and after treatment. Levels of NK cells, IFN-y and IL-12 were examined in blood samples before and four weeks after therapy began. There was a significant increase in NK cells and IFN-y and no difference in IL-12.8 Cordyceps sinensis mycelium extract, in combination with the endoparasitic fungus that commonly exists with C. sinensis, Paecilomyces hepialid, also had immune-stimulating activity in healthy adults. In this study, people were given 1.43g/day and after eight weeks the cytotoxic activity of NK cells was significantly higher than at baseline (before therapy.)9 Wild fruiting bodies of Cordyceps species are incredibly expensive and are therefore rarely, if ever used in research. However, It is likely that cultivated fruiting bodies have similar medicinal qualities.10,11,12

Another study with 52 healthy males and females aged 21-41 consumed either 5g or 10g of Lentinus edodes (shiitake mushroom) daily for four weeks. Eating the Shiitake for four weeks led to increased proliferation of NK cells and IgA, decreased CRP (a marker of inflammation), and an increase in IL-4, Il-10, TNF-α and IL-1. Serving size had no impact on cytokine levels, except that two servings of Shiitake increased serum IL-4.13 Shiitake is a good example of the dynamic effects that some mushrooms have on the immune system. Shiitake both increased inflammatory cytokines (IL-1, TNF-α) and anti-inflammatory cytokines (IL-10 and IL-4) simultaneously, illustrating the use of the term immunomodulatory: it is neither a pure stimulator nor a depressor of the immune system. This may mean that immune modulating mushrooms are safe and effective to take during both phases of the viral immune response, and in fact, may have inhibitory effects during the cytokine storm of acute respiratory distress syndrome.

Grifola frondosa (Maitake) also exhibits this modulating activity.  G. frondosa fruiting body extract produced both immune stimulatory IL-2, TNF-α and IFN-γ and suppressive IL-10 in breast cancer survivors taking 5-7g/kg per day of mushrooms extract for three weeks.14

The combination formula of Trametes versicolor(Turkey tail) and Salvia miltiorrhiza IMG_7864(Red sage root, or Dan Shen) given at 50mg/kg and 20mg/kg respectively for four months showed significant immunomodulatory effects in healthy adults. There was a significant increase in PBMC (peripheral blood mononuclear cells – NK, B and T cells) gene expression of IL-2 receptor, increase in T helper cells and the ratio of T helper cells to cytotoxic T cells. There is also a significant increase in IFN-γ.15 There is little information in western herbal and mycological medicine about the use of plant and mushroom combination formulas. Dan Shen is known to ‘move the qi of the blood’ and in combination with the immune stimulating activity of Turkey tail, has promise as a very useful combination for immune therapy.

Not all fungi are created equally as immune modulators. When the β-glucan isolate, lentinax, from L. edodes mycelium was administered to healthy adults, there was no difference seen in NK cells and inflammatory cytokines between treatment and control groups.16 This juxtaposes the previous Shiitake study where the subjects consumed whole mushrooms and did have immune stimulatory effects. Contrary to what has been suggested in in vitro research 17,18 a mushroom that showed no benefit in vivo was Agaricus blazeii. Healthy elderly women consumed 300mg of A. blazeii fruiting body extract three times daily for 60 days, and there was no change in levels of IFN-γ, IL-6 and TNF-α after administration.19 Perhaps the dose was too low in this study, further research is needed.

Mushroom Cytokine response Immune response (simplified) Phase of viral response most applicable
Grifola frondosa (Maitake) IL-10

IL-2, TNF-α, IFN- γ



Possibly severe phase

Prevention/incubation phase

Lentinus edodes (Shitake) IL-4, IL-10

TNF-α, IL-1



Possibly severe phase

Prevention/incubation phase

Cordyceps spp. IFN- γ Pro-inflammatory Prevention/incubation
Trametes versicolor (Turkey tail) with Salvia miltiorrhiza (Red sage) IL-2, IFN- γ Pro-inflammatory Prevention/incubation 

Mushrooms as immune-modulators

The increases seen in IL-10 and IL-4 after Maitake, Shiitake, and Cordyceps mycelium intake are important as they relate to TH2 immune responses. TH2 responses are anti-parasitic and anti-allergic, but through the lens of viral immunity and inflammation, are anti-inflammatory. In fact, IL-10 is considered an anti-inflammatory master regulator. 20,21,22,23 IL-10 is essential for defending the host from tissue destruction during acute phases of immune responses, though it is not as desirable in the initial phase of infection, where a higher TH1 (inflammatory) response is required. At this stage, IL-10 can downregulate antigen presentation in macrophages and dendritic cells and can lead to chronic infection.24 During the later stages of infection, however IL-10 levels can determine host survival and higher concentrations of IL-10 have been associated with better outcomes in patients with acute respiratory distress syndrome.25Cancer Cell Interactions

This is immune modulation. As depicted, mushrooms are neither solely inflammatory, nor anti-inflammatory, and so should be utilized as such. The safety of medicinal mushroom use at different phases of the immune response is debatable. It is most likely that if mushrooms and mushroom extracts are consumed as preventative medicine, and the immune response is primed, the host won’t succumb to infection in the first place. There is some concern that if IL-10 is too high during the initial phase, the infection will become chronic, but since the mushrooms are simultaneously stimulating inflammatory cytokines, this isn’t likely.

  TH1 TH2
Associated cytokines IL-2, IL-12, IFN-γ, TNF-α IL-4, IL-10, IL-5, IL-6, IL-13, IL-9


Mushroom Derived β-glucans and the Immune Response

The most studied immune-stimulating constituents derived from medicinal mushrooms are 1,3/1,6-β-glucans. β-glucans, or polysaccharides, are present in all mushrooms as they are an integral component of the mushroom cell wall. Macrophages in the gut have specific receptors for β-glucans, most significantly Dectin-1, complement receptor 3 and TLR-2.26,27 When β-glucans bind to these receptors, an immune response is initiated. Because of this, in most studies, polysaccharides have been deemed the ‘active’ constituents in regards to immune activation.  Therefore, isolation and administration of these compounds is most commonly seen in the literature.

Pleuran, a polysaccharide derived from Oyster mushrooms

There are a number of human trials exploring the use of pleuran, a polysaccharide extracted from Pleurotus ostreatus (Oyster mushroom) as a therapeutic agent in respiratory infections. As respiratory infections are most commonly of viral origin,28 it seems appropriate to discuss this research here. In a double-blinded, placebo-controlled, randomized multicentric study, 175 children treated with pleuran  experienced a significant reduction in the frequency of recurrent respiratory tract infections.29 These findings agreed with a Spanish study investigating 166 children aged one to ten years old who were also treated with pleuran for recurrent respiratory infection.30

Advantageous respiratory effects of pleuran are also observed in adult athletes. A study IMG_6690of 50 athletes treated with pleuran over a three month period found a significant reduction in the frequency of upper respiratory tract infections compared to athletes treated with placebo. Blood samples of the athletes showed significantly higher levels of circulating NK cells in the pleuran group as compared to the placebo group.31

Oyster mushrooms contain almost 33% polysaccharides,32 so we can deduce from these studies that consuming whole Oyster mushrooms and/or Oyster mushroom aqueous extracts could be beneficial for the prevention of respiratory infections.

Immune-stimulating polysaccharides in late stage cancer patients

The polysaccharides isolated from Ganoderma lucidum, also known as ‘Ganopoly’, were administered at 1800mg three times daily in late stage cancer patients, and there was a significant increase in NK cells, IL-1, IL-6 and IFN-γ after administration.33 Another isolate, polysaccharide krestin (PSK), is a protein-bound polysaccharide derived and isolated from Trametes versicolor. In a phase one clinical trial, breast cancer patients consumed 6 or 9g of PSK for six weeks, leading to an increase in CD8 T cells and NK cells.34 Another isolated polysaccharide, Maitake D fraction (derived from the fruiting body of G. frondosa), was administered to patients with stage 2-4 cancer aged 46-84 at doses between 40 and 150mg twice daily. IL-2 and NK cell activity was detected through peripheral blood draw and both were significantly increased after administration35 The research on isolated, mushroom-derived polysaccharides was intended to prove anti-cancer activity, but because of the close similarities of anti-cancer and antiviral immunity,36 it also suggests that polysaccharides support antiviral immunity in late stage cancer patients.

In vivo healthy animal trials

Polysaccharides from G. lucidum, L. edodes and G. frondosa administered to healthy mice significantly increase macrophage phagocytosis and NK cell activity.37 Other studies have demonstrated similar immune-enhancing effects on healthy mice with G. frondosa and L. edodes extracts exhibiting increases in IL-12, IL-6, and IFN-γ. In this study, the combination of the G. frondosa and L. edodes extracts have a stronger effect than either extract alone.38 Maitake D fraction increases IL-12 and IFN-γ in healthy mice along with a significant decrease in IL-4 and IL-10.39 C. militaris extract also increases IL-12 and TNF-α cell activity in H1N1 infected mice.40

In vivo animal cancer models

A number of in vivo animal trials explore different mushroom extracts with similar immune effects. Many of these animal studies are cancer models, so they will be mentioned briefly. Agaricus hot water extracts increase IFN-γ, IL-6 and IL-1,41,42 Reishi polysaccharide and triterpene extracts increase inflammatory NFkB, TNF- α, IL1-b, IL-2, IFN-γ 43,44,45,46 Maitake extract increases IL-12, IFN-γ and TNF-α, IL-147,48 and PSK increases IL-12.49 Ganoderma polysaccharides increase NK cells and cytotoxic T cells, IL-1, IL-6 and IL-1.50,51

Because these are cancer models, so it is not completely clear if the same effects would take place in healthy animal models, though we can deduct from other experiments using healthy volunteers and healthy animals that it is likely that similar immune effects would occur.

In vitro antiviral activity

There are a number of fungal constituents that have antiviral activity in-vitro, including polysaccharides, indole alkaloids, terpenoids, polyketides and lignan derivatives.  Agaricus subfruescens and Grifola frondosa act directly on viral particles, β-glucan protein from A. subfruescens inhibits viral adsorption into the cell,  polysaccharides from A. subfruescens and polysaccharopeptide from T. versicolor inhibit viral replication, and triterpenes from Ganoderma spp directly kill virus proteins.52

The fruiting body ethanol-water extract of T. versicolor extract increases the TH1-related cytokines IL-2, IL-12, IL-18 and IFN-γ.53,54 As most of the research done on T. versicolor is with an isolated constituent, PSK, it is significant that this study, which used whole fruiting body extract, exhibits immune stimulating qualities.

Maitake fruiting body extract does not show direct antiviral activity to influenza A but does exhibit antiviral activity through macrophage activation and an increase in TNF-α production. 55

L. edodes mycelium directly inhibits influenza virus growth at early phases of infection, possibly during the entry process of viral particles to host cells. The in vivo administration stimulated an increase in innate immunity as well, suggesting that Shiitake mycelium has antiviral effects through both inhibition of initial viral replication and immune stimulation.56

A little known mushroom, Cryptoporus volvatus, the Cryptic Globe Fungus, has shown cryptanti-viral activity through multiple mechanisms. Aqueous extracts of the fruiting body inhibit porcine respiratory syndrome virus infection by repressing viral entry, viral RNA expression, possibly viral protein synthesis, cell-to-cell spread, and the release of virus particles from the host cell. C. volvatus also inhibits influenza virus replication in vitro and in vivo.57,58,59

The aqueous extract of Phellinus igniarius, or Fire Sponge, shows virucidal activity against influenza A and B viruses, including 2009 pandemic H1N1, human H3N2, avian H9N2, and oseltamivir-resistant H1N1 viruses. The study concludes that this extract may interfere with one or more early events in the viral replication cycle, including viral attachment to the target cell. 60

In vitro research is what propels in vivo research forward, but it is important to take this information with a grain of salt and understand this is what may happen in the human body, and not necessarily what will happen.

Anti-neuraminidase activity

A highly valued antiviral action in pharmaceuticals is neuraminidase inhibition. This is the mechanism of the commonly known antivirals Tamilflu and Rilenza. Neuraminidase is found on the surface of influenza viruses and allows viruses to be released from the host cell so they can then infect other healthy human cells. Neuraminidase inhibitors have been shown to improve the outcome of patients with leukemia and influenza. 61 Medicinal mushrooms and their constituents have been shown to have neuraminidase phimg_7902inhibitory activity in vitro and in vivo. Ganoderic acids, triterpenes found in Ganoderma species, have broad spectrum inhibition against influenza neuraminidases, specifically H5N1 andH1N1.62,63 Both the fruiting body and mycelial extracts of Phellinus spp. have neuraminidase inhibiting actions as well. 64,65,66  While there is still more research needed in this area, it is possible that Reishi and Phellinus species could be beneficial in treating viruses that utilize neuraminidase.

This paper focuses on mushrooms as antiviral therapies for enveloped, influenza-like viruses, but there is in vitro evidence to suggest medicinal mushrooms have antiviral activity towards many different viruses.67,68 Ganoderma lucidum has shown to be active against enterovirus, 69 human papillomavirus (HPV),70,71 herpes simplex virus (HSV)72,73,74,75 hepatitis B (HBV)76 and Epstein Barr virus (EBV).77 Cordyceps militaris has anti-hepatitis C (HCV) activity.78 Trametes versicolor is active against human immunodeficiency virus HIV.79.80 Grifola frondosa is active against HSV-181 and HBV.82 Inonotus obliquus has anti-HSV, 83,84 anti-HCV 85and anti-HIV86 activity and Lentinula edodes has anti-HBV 87 and anti-HSV 88 activity. Although not explored in this paper, these antiviral actions are interesting and worth considering for further dissection in future research.

Having a basic understanding of our complex immune system is important in understanding the role that mushrooms play as antivirals. As we have seen, mushrooms are immune modulators and can stimulate inflammatory and anti-inflammatory responses simultaneously. Mushrooms are most likely to be useful as preventative medicine before infection occurs, though if there is an initial infection, Cordyceps, Maitake, Shiitake, Turkey tail and Oyster mushroom may prevent infection from becoming more severe. If infection does become severe, the mushrooms that also stimulate IL-10 – Maitake, Cordyceps and Shiitake, could also be beneficial. In the wake of the current viral pandemic, these mushrooms should be further explored and utilized as medicine. Further research is essential in elucidating their potential effects.

antiviral mechanisms of medicinal mushrooms


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  87. Zhao YM, Yang JM, Liu YH, Zhao M, Wang J. Ultrasound assisted extraction of polysaccharides from Lentinus edodes and its anti-hepatitis B activity in vitro. Int J Biol Macromol. 2018;107(Pt B):2217–2223. doi:10.1016/j.ijbiomac.2017.10.100
  88. Santoyo,Susana, Ramirez-Anguiana Ana, christina Aldaris-Garcia L et al. Antiviral activities of Boletus edulis, Pleurotus ostreatus and Lentinus edodes extracts and polysaccharide fractions against Herpes simplex virus type 1. Phys Rev Lett. 2002;88(12):4. doi:10.1103/PhysRevLett.88.126404











Oxalates and Fungi

Cause for concern?

The most common manifestation of kidney stones is without a doubt, calcium oxalate stones – 80% of stones, to be exact. For this reason, people who are prone to stones tend to avoid high oxalate-containing foods. The most popular oxalate-rich delicacies: spinach, beets greens, chard, chocolate, tea, nuts, grains, and yes, some mushrooms. It is important to keep in mind that not all oxalate-rich foods will lead to kidney stones – chemistry is much more complex than that.

There was a recent report1 about an older Japanese woman with liver cancer who consumed 4-5 tsp of Chaga mushroom per day for 6 months, and happened to get nephrotoxicity. The postulated culprit: Chaga mushroom. Unfortunately, in this study, there was neither mention of the source of the Chaga, if this was the canker or mycelium, nor if the Chaga powder was an extract or not. This case report concluded that it must have been the high oxalate content in the Chaga mushroom that induced this nephrotoxicity.  Is this a true cause or simply a correlation? Should consumers be concerned about the oxalate content in in all Chaga products?

My hope is that this post will be educational, and readers will walk away with some answers to these questions.

This report got me thinking, about Chaga and oxalates and wondering, could this really be? I mean, they do look so similar. Could this be an example of the doctrine of signatures or is it possible that if you crush any golden substance into small enough pieces it may resemble calcium oxalate fragments? (No offense to the doctrine of signatures)

Some education about oxalates

First, not all oxalates are created equal. There are soluble and insoluble oxalates. Insoluble oxalates are already bound to minerals, for example: calcium oxalate, magnesium oxalate and iron oxalate. The insoluble oxalates in foods pass right into the GI and come out in feces. They will not be absorbed in the blood stream, and so they are not a concern for causing hyperoxaluria (high urine oxalates). Examples of soluble oxalates are potassium and sodium oxalate. Unlike soluble oxalates, these acids release free oxalate anions which can pass into the blood stream. Free oxalate can then bind with free calcium and make calcium oxalate crystals;

This distinction is important to keep in mind when considering high oxalate foods.

Mushrooms and Oxalates

White button mushroom and Shiitake mushroom are both very high in oxalates, but 99% of them are insoluble! So, don’t fret about these mushrooms – the oxalate will all come out in your shiit(ake).2

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Oyster mushrooms, on the other hand, are moderately high in oxalates, and 90% of them are soluble. They contain a comparable amount to chocolate, almonds, and grains.2 So if you can eat more oyster mushrooms than you can chocolate, you are my hero and you may want to eat them with some calcium containing foods – more about this later.

Pleurotus ostreatus

Lucky for kidney stone formers, they can continue to consume large quantities of Lion’s Mane (Hericium erinaceus), Cauliflower mushroom (Sparassis spp) and Reishi (Ganoderma spp). There are no soluble oxalates found in any of these mushrooms.2

Remember, for an organism to take the time and energy to make a molecule, the molecule must serve some purpose for that organism; oxalates are not made to cause kidney stones in humans. I hope to find more on this subject in relation to mushrooms, but for now, I found one study. According to this study, calcium oxalate crystals form in response to toxic metal stress.3 So perhaps mushrooms growing in environments where there are more toxic metals will in turn have a higher calcium oxalate load than those same species growing elsewhere.

Oxalates and Chaga

Oxalate samples were assessed in Chaga samples from Russia, Finland and Thailand. A hot water extract was made of the Chaga canker (the growth coming out of the tree, traditionally used as medicine) and oxalate content was assessed. Researchers found that for 1 gram of the Russian Chaga extract there was 97.6mg of soluble oxalic acid and 24mg of insoluble oxalic acid. The Finnish Chaga extract contained 55.62mg/g of soluble oxalates and 9.5mg/g of insoluble oxalates. Japan Food Research Laboratories measured oxalate content of the mushroom powder and concentrations of 11.2g total oxalate in 100g of powder. Another test from this laboratory on a separate Chaga sample was 2.8g/100g.1

Some perspective: These amounts are higher than most edible mushrooms, similar to the amount in almonds, peanuts, cereal grains and chocolate, and much lower than what is found in high oxalate foods like spinach, rhubarb and beet greens.4

Cooking and Oxalates

Oxalate load was compared in a 10g sample of dried mushrooms cooked versus not cooked. This study found that cooking slightly decreases oxalates, but also seems to increase them in certain cases. Interestingly, levels of soluble oxalate from forest harvested mushrooms was generally lower than cultivated mushrooms.2

Concerned about your mushroom intake and risk of kidney stones?

Here is some food for thought:

Calcium intake and oxalate absorption

People with low calcium diets can benefit from consuming calcium-containing foods along with oxalate-containing foods to decrease oxalate absorption. One study found that exogenous (dietary) calcium leads to a linear reduction of oxalate absorption within the range of daily intake of 200-1200mg of calcium.  This case has been documented in numerous studies5,6,7 and calcium supplements have been shown to lower the oxalate absorption. One study assessed this theory using 1000mg calcium supplement given simultaneously with soluble oxalates. They concluded that this technique will reduce oxalate absorption by 10%, however this is mostly effective if the person already has a low calcium diet.  When calcium is supplemented to an already high calcium diet, there is only a 1% decrease in oxalate absorption.


Perhaps this is an excellent reason to add milk to tea and coffee and of course, to your favorite mushroom drink. To give some perspective, 1 cup of dairy milk has about 305mg of calcium and 1 cup of fortified almond milk has about 300mg of calcium.

The microbiome and oxalate absorption

Within the microbiome resides a bacteria known as Oxalobacter formigenes.8  This superlative gut bacteria degrades oxalates and helps to prevent hyperoxaluria and kidney stones. So, for those concerned about the oxalate content in the mushrooms discussed, perhaps this little bacteria is your ally. Studies looking at oral intake of Oxalobacter  have shown less urinary oxalate excretion following administration of an oxalate heavy food load compared to when there was no Oxalobacter administered. Unfortunately, this bacteria is susceptible to antibiotic use. Specifically, clarithromycin and doxycycline have been shown to annihilate this little probiotic, leaving the human left behind to be more susceptible to kidney stones.


Representation of Oxalobacter formigenes activity. Utilizes oxalate as a source of energy through the oxalate-formate antiporter.9

This is all very interesting and something most people do not need to worry about. Though I would say, if you are an oxalate kidney stone former: don’t eat a ton of oyster mushrooms or drink multiple cups of Chaga tea per day. Do make sure to drink plenty of water and eat a diet with adequate amounts of calcium, and hope that antibiotic use hasn’t eradicated all of your Oxalobacter.


Work Cited

  1. Kikuchi Y, Seta K, Ogawa Y, et al. Chaga mushroom-induced oxalate nephropathy. Clin Nephrol. 2014;81(6):440-444. doi:10.5414/CN107655
  2. Savage GP, Nilzen V, Österberg K, Vanhanen L. Soluble and insoluble oxalate content of mushrooms. Int J Food Sci Nutr. 2002;53(4):293-296.doi:10.1080/09637480120057000
  3. Jarosz-Wilkolazka A, Gadd GM. Oxalate production by wood-rotting fungi growing in toxic metal-amended medium. Chemosphere. 2003;52(3):541-547. doi:10.1016/S0045-6535(03)00235-2
  4. Glamočlija J, Ćirić A, Nikolić M, et al. Chemical characterization and biological activity of Chaga (Inonotus obliquus), a medicinal “mushroom.” J Ethnopharmacol.2015;162:323-332. doi:10.1016/j.jep.2014.12.069
  5. Von Unruh GE, Voss S, Sauerbruch T, Hesse A. Dependence of oxalate absorption on the daily calcium intake. J Am Soc Nephrol. 2004;15(6):1567-1573.doi:10.1097/01.ASN.0000127864.26968.7F
  6. Bong WC, Vanhanen LP, Savage GP. Addition of calcium compounds to reduce soluble oxalate in a high oxalate food system. Food Chem. 2017;221:54-57. doi:10.1016/j.foodchem.2016.10.031
  7. Brogren M, Savage GP. Bioavailability of soluble oxalate from spinach eaten with and without milk products. Asia Pac J Clin Nutr. 2003;12(2):219-224.
  8. Duncan SH, Richardson AJ, Kaul P, Holmes RP, Allison MJ, Stewart CS. Oxalobacter formigenes and its potential role in human health. Appl Environ Microbiol.2002;68(8):3841-3847. doi:10.1128/AEM.68.8.3841-3847.2002
  9. Corica, Domenico & Romano, Claudio. (2015). Renal Involvement in Inflammatory Bowel Diseases. Journal of Crohn’s & colitis. 10. 10.1093/ecco-jcc/jjv138.
  10. Oxalates in Chaga – A Potential Health Threat By Michael W. Beug, Chair NAMA Toxicology Committee
  11. Mitchell T, Kumar P, Reddy T, et al. Dietary oxalate and kidney stone formation. Am J Physiol Renal Physiol. 2019;316(3):F409–F413. doi:10.1152/ajprenal.00373.2018