Therapeutic dosing: Higher doses, often more frequently throughout the day
Maintenance: Lower doses, often less frequently throughout the day
The concept of therapeutic and maintenance dosing is based on the theory of ‘trained immunity’ (1,2). This theory suggests that ongoing, high doses of ß-glucan-rich mushrooms are not, in fact, necessary to potentiate immune modulation and protection from infections. The innate immune system, or the “first responders,” has the ability to create non-specific memory responses to a variety of subsequent infections after a primary infection or vaccination. For example, a person may become infected with a specific pathogen (virus, bacteria or fungi) and the innate immune system will mount a response to that specific pathogen. Additionally, innate memory cells will remain that can help protect against that same infection in the future, as well as other unrelated infections, i.e. a non-specific memory response. These changes in immune memory have been observed for as long as one year following initial administration of ß-glucans (3). These innate memory cells have a relatively short lifespan, and so it seems unlikely that trained immunity would last as long as it does. However, researchers have discovered that ß-glucans not only induce trained immunity in mature innate immune cells, but they also alter the cells hematopoietic progenitors (cells that will eventually differentiate into innate immune cells) within the bone marrow leading to the prolonged presence of trained monocytes and macrophages in circulation (4). The ß-glucans are essentially playing a role in your immune cells’ epigenetic purpose.
Initial higher dosing of ß-glucan-rich mushrooms is like an immune training program. Similar to building muscle, the initial training takes a little longer, and you have to train more often. Maintaining muscle is much easier than building muscle, and sometimes once a week training is all that is needed for muscle maintenance. Similarly, taking mushrooms one to two times per day, and maybe even a few times per week, is all that is needed for immune maintenance.
Initial dosing during the therapeutic phase for immune modulating effects should be done repeatedly, ideally three times per day. One study comparing the duration of the effect of oral dosing versus intravenous dosing of ß-glucans found that the repeated oral dosing “clearly resulted in stronger and longer action stimulation (5).” Intravenous dosing of ß-glucans is mostly available in clinical trials outside of the United States and is not yet common practice in the U.S. Therefore, repeated oral dosing two to three times per day is most likely to optimize initial immune benefits.
When dosing mushrooms like lion’s mane, tremella and oyster mushroom for neurocognitive benefits, the idea of immune training or cellular training does not apply. In the majority of studies exploring the neurocognitive benefits of lion’s mane, researchers have found that many benefits relating to memory and mood were no longer present after discontinuation of supplementation. It is important to note, however, that certain patterns related to mood may be a result of “negative neuroplasticity.” Negative neuroplasticity is the idea that getting stuck in a particular maladaptive pattern, like insomnia, can create neural patterns that are then primed for insomnia. Changing certain behaviors or taking certain medications and/or supplements can help to rewire negative patterns. Mushrooms with neurological actions, such as BDNF-mediated neurogenesis, may help to rewire negative plasticity, and therefore may not be needed on a daily basis as previously thought. While this may be true for mood-related disorders, it is unlikely to be the case for memory and cognitive enhancement. Either way, once daily dosing seems adequate for neurocognitive effects.
Mushrooms are composed of many different constituents. These constituents have different physiological activities that are fully dependent on whether they are absorbed, or not absorbed, into the bloodstream from the intestines.
The immune-modulating benefits of mushrooms are dependent on a healthy environment within the small intestine, where there are groups of immune cells within the gut-associated lymphoid tissue (GALT). The GALT contains pockets of immune cells called Peyer’s patches which contain M cells, and M cells present ß-glucans to innate immune cells like macrophages and dendritic cells via specific cell-surface receptors, most notably dectin-1, but also TLR2 and CR3. Mushroom ß-glucans bind to dectin-1 and stimulate an immune response throughout the bloodstream, lymphatic system, spleen, bone marrow, and lymph nodes.
It is important to note, however, that not all ß-glucans are absorbed into the bloodstream, and that some make their way to the large intestine. Mushroom ß-glucans are prebiotics, acting as food for healthy gut microbes and improving the intestinal microenvironment (6). A healthy intestinal microenvironment is fundamental to human health and research has shown that microbial fermentation of fungal ß-glucans can increase important post-biotic short chain fatty acids like butyrate (7). Improving the intestinal microenvironment does not result in trained immunity, like small intestinal absorption of ß-glucans does, so for prebiotic benefits, daily dosing seems best.
Food. If there is a lot of food in the small intestine, there will be less surface area for the ß-glucans to come into contact with M cells, and the immune response will likely be less significant than it would be on an empty stomach.
Alcohol. Chronic alcohol consumption has been shown to alter the innate immune system at the level of the Peyer’s patch (8). Frequent alcohol intake may lessen the immune benefits of mushroom ß glucans.
Tannins/polyphenols. Blending and emulsifying ß-glucans with tannin-rich substances like coffee, tea and chocolate create a tannin-polysaccharide complex. However, the bonds between polysaccharides and polyphenols are hydrogen bonds and are easily impacted by temperature and pH (acidity). Bonds can be broken at high temperatures between 68°F-104°F, so if blending mushroom powders with tannin-rich foods, blend at higher temperatures rather than cold. If polysaccharides are contained in these complexes when they reach the small intestine, they will not be available to bind immune receptors in the GALT and their immune-modulating properties will likely be nullified (9).
Moerings, B. G. J., de Graaff, P., Furber, M., Witkamp, R. F., Debets, R., Mes, J. J., van Bergenhenegouwen, J., & Govers, C. (2021). Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.672796
Garcia-Valtanen P, Guzman-Genuino RM, Williams DL, Hayball JD, Diener KR. Evaluation of trained immunity by β-1, 3 (d)-glucan on murine monocytes in vitro and duration of response in vivo. Immunol Cell Biol. 2017 Aug;95(7):601-610. doi: 10.1038/icb.2017.13. Epub 2017 Feb 23. PMID: 28228641; PMCID: PMC5550561.
Moorlag SJCFM, Khan N, Novakovic B, Kaufmann E, Jansen T, van Crevel R, Divangahi M, Netea MG. β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1. Cell Rep. 2020 May 19;31(7):107634. doi: 10.1016/j.celrep.2020.107634. PMID: 32433977; PMCID: PMC7242907.
Mitroulis I., Ruppova K., Wang B., Chen L.S., Grzybek M., Grinenko T., Eugster A., Troullinaki M., Palladini A., Kourtzelis I. Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell. 2018;172:147–161.e12.
Vetvicka, Vaclav & Vetvickova, Jana & Ms,. (2008). A Comparison of Injected and Orally Administered β-glucans. 11.
Nowacka-Jechalke N, Juda M, Malm A. The preliminary study of prebiotic potential of Polish wild mushroom polysaccharides: the stimulation effect on Lactobacillus strains growth. Eur J Nutr. 2018 Jun;57(4):1511-1521. doi: 10.1007/s00394-017-1436-9. Epub 2017 Mar 28. PMID: 28353071; PMCID: PMC5959981.
Mitsou EK, Saxami G, Stamoulou E, Kerezoudi E, Terzi E, Koutrotsios G, Bekiaris G, Zervakis GI, Mountzouris KC, Pletsa V, Kyriacou A. Effects of Rich in Β-Glucans Edible Mushrooms on Aging Gut Microbiota Characteristics: An In Vitro Study. Molecules. 2020 Jun 18;25(12):2806. doi: 10.3390/molecules25122806. PMID: 32570735; PMCID: PMC7355846.
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
Proving that mushrooms are an essential part of the human diet
Definitions to consider while reading:
Antioxidant: Compounds that mitigate oxidation. Oxidation is a reaction that can produce free radicals, leading to cellular damage. Antioxidants such as thiols and ascorbic acid (vitamin C) terminate these reactions by donating electrons. To balance oxidative states, living organisms maintain systems with overlapping antioxidants such as glutathione, catalase, superoxide dismutase.
Blood-brain barrier: a filtering mechanism of the capillaries that carry blood to the brain and spinal cord tissue, blocking the passage of certain substances.
Cation chelator: a type of bonding of ions and molecules to metal ions. There is application of this in removing toxic metals from the body.
Glutathione: Glutathione is a tripeptide (cysteine, glycine, and glutamic acid) found in surprisingly high levels—5 millimolar—concentrations in most cells. Responsible for the following actions in the body: (Pizzorno)
Direct chemical neutralization of singlet oxygen, hydroxyl radicals, and superoxide radicals
Cofactor for several antioxidant enzymes
Regeneration of vitamins C and E
Neutralization of free radicals produced by Phase I liver metabolism of chemical toxins
One of approximately 7 liver Phase II reactions, which conjugate the activated intermediates produced by Phase I to make them water soluble for excretion by the kidneys
Transportation of mercury out of cells and the brain
Regulation of cellular proliferation and apoptosis
Vital to mitochondrial function and maintenance of mitochondrial DNA (mtDNA)
Lipid peroxidation: The oxidative degradation of lipids. It is the process in which free radicals “steal” electrons from the lipids in cell membranes, resulting in cell damage. (Wik)
Oxidative stress: disturbance in the balance between the production of reactive oxygen species (free radicals) and antioxidant defenses (Betteridge)
I am not necessarily a fan of isolation and ‘constituentism’ in supplemental medicine – especially when a constituent has been isolated from its synergistic community of molecules from the whole plant or whole mushroom and is considered supposedly different than a pharmaceutical. Though, I do love to understand the individual constituents in organisms and how they work independently, in order to better understand how they work synergistically. There is also a greater understanding to be had of how animals, plants, fungi and bacteria all evolved together when we can explore specific plant and fungi constituent mechanisms with specific cellular receptors and transporters in the animal organism. A specific example of this is a compound called Ergothioneine (ERG). ERG is an amino acid derivative, specifically a crystalline betaine, derivative of histidine – the etymology explains; ergot- (found in ergot (fungus) thione- (double bond to a Sulphur) and -ine (amine containing)—basically a sulphur containing amine found in fungi. ERG is also found in Actinobacteria (gram positive bacteria that behave similar to fungi in soil, helping to decompose the organic matter of dead organisms so the molecules can be taken up by new plants, they even grow extensive mycelium like fungi and were in fact long believed to be fungi) and Cyanobacteria, commonly known as blue-green algea, (another abnormal bacteria that can actually obtain their energy from photosynthesis – they are the only photosynthetic prokaryote able to produce oxygen). (blankenfeldt)
Specific ERG transporters in the animal
We have evolved so closely with mushrooms that we have specific transporters and receptors uniquely for mushroom compounds. ERG is no exception. While we have a specific receptor for ERG, we cannot synthesize this molecule ourselves, and as I will describe later, we are discovering this compound is extremely important for human health. The ERG transporter, OCTN1, (gene: SLC22A4) is found specifically on erythrocytes, fetal liver and bone marrow, ileum of the small intestine, trachea, kidney, cerebellum, lung, monocytes, seminal vesicles and the lens and cornea of the eye (Halliwell). Interestingly, ERG transporter is concentrated in the mitochondria of cells – suggesting a role in protecting mitochondrial components from DNA damage (Paul, Halliwell). This transporter’s only known role is to sequester as much ERG within the cells as is available, and only cells with this transporter can absorb, distribute, and retain this compound (Grundermann). Researchers explored the effects when cells were depleted of this transporter, the results being that cells were more susceptible to oxidative stress, leading to mitochondrial damage, protein oxidation, and lipid peroxidation. Once taken up into the cell, ERG is extremely bioavailable and is retained for up to a month within the body.
Bioavailability of ergothioneine from mushroom consumption
Once consumed in the diet, whether it be the isolated molecule or from whole mushrooms, ERG is quickly absorbed into the blood stream. Human erythrocytes (red blood cells, RBC) contain 2-9 fold more ERG than plasma. Interestingly, concentration is lowest in early life (1-10yo), increases between 11-18yo and reaches maximum value of 3.7mg/100mL by age 18. In this study, subjects consumed 8g and 16g of mushrooms and increases in red blood cell ERG were observed. After 1 and 4hr of consumption, the 16g mushroom dose increased RBC ERG concentration compared to the control, and after only 2 hrs of 16g of mushroom consumption, RBC ERG concentration was significantly higher than the control. Variability in bioavailablity was due to genetic variations in the SLC22A4 gene (Heller, Kris-etherton, Beelman). Interestingly, mutations in the ERG transporter have been identified as a susceptibility factor for autoimmune disorders, such as rheumatoid arthritis and Crohn’s disease, as well as neurodegenerative disorders, such as dementia and Parkinson’s (Paul, Snyder).
Why do we care – Once ergothioneine is in the cell, then what happens?
Ergothioneine as an antioxidant and cytoprotectant: The distribution of ERG transporters may seem random, but on closer inspection, they seem to be present in tissues predisposed to high levels of oxidative stress and inflammation (Halliwell). In animal studies, animals who were completely deficient in ERG had higher levels of reactive oxygen species and were therefore more susceptible to oxidative stress. In vitro, ERG is a powerful scavenger of hydroxyl radical and has been shown to deactivate singlet oxygen at a higher rate than glutathione (Hseu, Servillo). Similar results were proven in vivo – rats supplemented with ERG had lower levels of lipid peroxidation and higher levels of glutathione and alpha-tocopherol. As one might surmise, ERG and glutathione seem to have an intimate relationship within the cell. Glutathione is considered the major intracellular antioxidant in almost all organisms and has important functions in detoxification and immune function. It has been proposed, based on current research, that ERG can help maintain GSH levels in the presence of oxidative burden by interacting with other cellular defense systems. The maintenance of glutathione tissue levels is important in maintaining health as depletion will impair immune function. Conveniently, mushrooms contain both glutathione and ERG. In fact, mushrooms have been observed to have higher GSH amounts than any vegetable or fruit. Grifola frondosa (Maitake), Hericium erinaceus (Lions mane), Pleurotus ostreatus (Oyster mushroom), Boletus edulis (porcini) and Lentinus edodes (shitake) containing the most, respectively (Kalaras). Considering the relationship between ERG and GSH in mushrooms, a correlation analysis found that mushrooms high in GSH were also high in ERG, specifically the caps or pileus of the mushrooms (kalaras). All this said, mushrooms are an important source for cellular antioxidants.
Cation chelator: ERG chelates divalent metal cations – specifically, Cu2, hg, Zn, Cd, Co, Fe, and Ni (Cheah, Song, Kerley). Binding these cations in the body may help prevent their participation in the generation of reactive oxygen species. For example, EGT has been found to protect DNA and protein against copper induced oxidative damage through formation of a redox-inactive EGT-Cu complex. Interestingly, the high levels of ERG in semen – due to the high concentration of ERG OCTN1 transporter on the seminal vesicles- have been shown to prevent Cu inhibition of sperm motility. There is more to be explored between the relationship of ERG and semen viability.
Ergothioneine, aging, and cognitive decline: As we age, we are more vulnerable to the oxidative stress and environmental toxins that slowly damage our DNA, making us more susceptible to neurodegeneration – one of many conditions associated with DNA damage from oxidative stress. Low levels of glutathione have been linked to certain neurodegenerative diseases including Parkinson’s disease (Wei, Shah). ERG was able to dose dependently enhance glutathione activity in the rat liver cytosol—leading researchers to postulate that declining ERG may play a role in age related decline of GSH and glutathione peroxidase. Furthermore, ERG levels were found to be lower in the elderly with early stages of dementia and in PD patients relative to age matched healthy controls (Cheah). In animal studies, oral administration of ERG protected neurons and preserved cognitive function following administration of toxic amyloid beta cisplatin or D-galactose. It is now understood that the presence of Octn1 transporter in the blood brain barrier is responsible for these neuroprotective actions. Captivatingly, researchers found that there is a direct relationship between whole blood and brain ERG levels following consumption (Cheah). It is rare for compounds to be bioavailable in this way and transported across the blood brain barrier so readily – even glutathione needs to be taken intranasal for treatment of neurodegeneration.
Ergothioneine human trial: uptake metabolism and effects
While there is undeniably a lack of human trials exploring the in vivo effects of ERG, a recent study from 2017 explored ERG uptake, metabolism, and effects on biomarkers of oxidative damage and inflammation in healthy human subjects (cheah, Tang). One of the most interesting aspects of ERG discussed in this particular article is that ERG is a tautomer. This means that it exists in two forms – thione and thiol. The thiol is a single bond to sulfur and the thione is a double bond to sulfur. The article explains that in animal physiologic conditions, ERG primarily exists as the thione tautomer – under circumstances of low stress in the body, ERG remains in its thione tautomer form and is not the first choice as an antioxidant, rather endogenous antioxidants like glutathione are preferred (glutathione is a primary antioxidant thiol in the body). When the cells undergo higher levels of oxidative stress, ERG transforms into its thiol tautomer form and is then used for extra support. Additionally, under levels of elevated stress, tissues have increased amounts of the ERG, supposedly by upregulating expression of the OCTN1 ERG transporter in response to inflammatory cytokines.
This study also found that ERG can be stored in the cells for up to a month. It is theorized that ERG is stored for an extended period of time following consumption until it is required as a stronger defense mechanism.
During administration of ERG, plasma levels significantly elevated, while whole blood levels steadily increased for up to four weeks after administration stopped (red blood cells could continue to take ERG up as needed), and the excretion of ERG in the urine remained low, indicating that ERG is absorbed and retained in the body after oral administration. While this study used pure ERG, other studies previously mentioned (Heller) prove this same high bioavailability of ERG from dietary mushrooms, and so I will consider this as true for dietary ERG.
Mushroom analyses of ergothioneine: Fruiting body or mycelium? Gilled mushrooms or polypore mushrooms?
ERG was highest in the fruiting body of Pleurotus ostreatus and in the mycelium of Pleurotus eryngii. Generally, fruiting bodies and mycelium contained different amounts of ERG, with Pleurotus genus containing the highest amounts overall (Chen). Among simple mushrooms, fruiting body of White Button had the least (1.4mg erg per 85g mushroom) and Portabella the highest (2.7mg erg per 85g mushroom). While among specialty mushrooms, Maitake had the least (16.3mg erg per 85g mushroom) and oyster the highest (26.4mg per 85g mushroom) (Dubost).
Fruiting bodies of gilled mushrooms, specifically the cap, contain the most ERG, while polypore mushrooms contain very small amounts. Interestingly, the mycelium of Ganoderma contains more ERG than the fruiting body, but still not as much as the fruiting bodies of Shitake, Matsutake, Oyster, and Maitake (Lee, Wang).
Hot water extraction is sufficient to extract ERG from mushrooms.
In a study that explored water extraction – temperature of water, ratio of water to mycelium and the extraction rate of ERG, the following information was found:
Most notable: at 85°C and 20:1 ratio of mycelium to water, the extraction rate of ERG was 91.2% – the least effective yield of ERG was at 78°C and a 20:1 ratio of mycelium to water. There was no difference in ERG concentration between 5 minutes and 120 minutes, so a long boil to extract EGR is not necessary (Zhang).
Ergothioneine is a water soluble compound that is most abundant in Oyster mushrooms. There are transporters on different tissues in the body that are highly specific to ergothioneine. Ergothioneine is readily absorbed into the blood after consumption of mushrooms and stored in tissues for up to 1 month. In times of excessive oxidative stress, ergothioneine is taken up by those tissues and used as an antioxidant. Of note: there are transporters on the blood brain barrier and there is an association with low ergothioneine and age-related cognitive decline. In a world full of environmental toxins that are mostly impossible to escape, we might as well eat more mushrooms and get some extra protection.
How to apply this information to your life:
Eat a lot of mushrooms, especially Oyster mushrooms.
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Forget about the idea that mushrooms have chemicals that have pharmacological potential. Forget that you want to learn about the mushrooms so that you can ‘use’ them.
Just for a moment, let’s see the mushrooms as their own organism.
Their own organism with all of their chemicals not for the human system, but for the fungal system.
Every constituent that we wish to extract and isolate and identify has an important role within the living mushroom, and a role within the entire ecosystem.
Let’s explore these compounds and their functions within the mushroom before exploring their functions and relations within the human system.
Remember, a human is not their cholesterol, a human is not their pheromones, a human is not their amino acids. A human is a synergistic organism made up of thousands of molecules and cells all working together. It is impossible to understand who a human is from just analyzing one of these molecules.
When we look at the mushroom through the lens of its parts, keep in mind it is the synergism between these parts that makes the organism, not the isolated constituents.
The purpose of this writing is to first investigate major myco-constituents that have been researched for their medicinal value and understand their innate role in the fungal organism. After delving into the mushrooms on a cellular level I’ll discuss how these constituents interact with the human system. We did after all evolve with the mushrooms, we just work so beautifully together. Through understanding the innate role of these compounds and where they are within the mushroom organism, we gain insight into the best ways to extract these compounds to support our own physiology. Specific constituents that will be discussed: Polysaccharides, volatile compounds (Alcohols, monoterpenes, sesquiterpenes, aldehydes, ketones), triterpenes, ergosterol, phenolic compounds, and fatty acids.
The cell wall is an exquisite and imperative structure in all organisms. The cell wall role in fungi is similar to the role of the cell membrane in humans – it is dynamic in controlling the shape and protecting the organism from the environment. The cell well is made up of compounds involved in morphogenesis, reproduction, cell-cell and cell-matrix interaction. The fungal cell is rigid as it is made up of one of the hardest substances, chitin. Although rigid, it must also be complex to allow for budding, growth and adaptation to environmental stress. The fungal cell wall is composed of multidimensional, communicating polysaccharides including chitin and glucans. (Taborda)
– Many simple sugar molecules attached to one another, referred to as glucans when it is glucose molecules-
In the Mushroom
These chains of sugars may be extracellular (outside the cell wall), may be associated with the cell wall and membrane, or may be intracellular. Extracellular polysaccharide function is unclear, pullulan a polysaccharide similar to glycogen and mycodextran are alpha linked glucans that are extracellular. From what I could gather, the function of these may be as storage reserves. Beta 1,3 and beta 1,6 glucans are also sometimes found on the outside of the cell, but are most often important components of the cell wall itself. (Griffin) The major role of polysaccharides is in providing cell wall structure. As Basidiomycota (fungi with fruiting bodies) grow and mature fruiting bodies, the total polysaccharide levels increase. (Friedman)
With this knowledge about the role of these compounds as structural support and barrier to the fungal cell we can understand the role within the human organism.
In the Human
The polysaccharides act in the human in an analogous way as they act in the fungal cell. They support the human cells in responding to environmental stressors within the human terrain.
Polysaccharides play a number of functions in the human system. Once ingested, these compounds move through the GI, coming into contact to mucous membranes all the way down through the inner tube from mouth to anus. The mucous membranes have lymphoid tissue called gut associated lymphoid tissue (GALT) that contains immune cells called macrophages. These macrophages, or big eaters, are an important part of our innate immune system. These immune cells have specific receptors for beta-glucans, Dectin-1 and TLR2. Once the beta- glucans come into contact with them, there are chemical messengers called cytokines that are stimulated. Specifically, IL-12 and IFN-y. These cytokines are important in stimulating Natural killer cells, Cytotoxic T cells and TH1 cells. Once these cells are stimulated they target viruses and cancer cells. (guggenhein)
Polysaccharides also function as soluble fiber. When they enter the gut, they slow the release of glucose into the blood stream, acting as hypoglycemic compounds. They also help to decrease cholesterol through binding bile acids. When bile acids end up in the soluble fiber, they are pooped out and then the body will use cholesterol to make more, rather than recycling the bile acids. Along with binding bile acids, they also prevent absorption of cholesterol from food in the GI, further lowering serum cholesterol. These polysaccharides are also beneficial in controlling blood sugar. Polysaccharides inhibit the enzyme, alpha-glucosidase, this enzyme is known to induce after meal hyperglycemia. Along with inhibiting this enzyme, polysaccharides have also been shown to upregulate the GLUT 4, insulin-response glucose transporter, while down regulating NFkappa-B, a nuclear transcription factor that controls regulation of inflammation. (friedman, shamtsyan)
Polysaccharides as antioxidants: Polysaccharides increase activities of liver oxidative enzymes, catalase, glutathione peroxidase, and superoxide dismutase and increase glutathione and malondialdehyde levels. This is all to say that these compounds support our innate antioxidant systems supporting the human in relieving oxidative stress and free radical damage.
Polysaccharides as prebiotics: The oligosaccharides and polysaccharides contained in mushrooms are consumed by Bifidobacterium and Lactobacilli, two important bacteria in a healthy microbiome. Through supporting a healthy gut microbiome, this can also be helpful with asthma, allergies, anxiety and even depression.
Hot water – 100 degrees C for at least 2 hours
Volatiles Compounds and Triterpenes
Low molecular weight, carbon based compounds that vaporize at about 20 degrees Celsius. Include: Alcohols, monoterpenes, sesquiterpenes, aldehydes, and ketones
Triterpenes have 30 carbons and are too heavy to be volatile, but I put them here since they are made in the same pathway as monoterpenes and sesquiterpenes.
In the Mushroom
These volatile compounds are derived from primary and secondary metabolism pathways; they diffuse through the atmosphere as “infochemicals”
These chemicals function as attractants and deterrents to insects and other invertebrates. Fungal volatiles have important properties as pheromones and defense. Some of these compounds are an efficient way of defending against fungal feeders. Octanol, often called mushroom alcohol, is an alcohol that deters banana slugs from eating mushrooms while also serving as an attractant for fungus eating beetles. Amusingly, octanol from human skin serves as a host odor cue that attracts blood sucking insects. Trametes versicolor is an example of a polypore mushroom that produces sesquiterpenes: specifically, cardinene, beta guiaene, isoledene and gamma patchoulene that attract fungivorous beetles. (morath,Rosecke) Through attracting these insects the mushrooms are better able to spread their spores and inoculate nearby substrate. A good way to make more of themselves!
Monoterpenes, sesquiterpenes and triterpenes are all compounds in mushrooms that have a cholesterol backbone. (The chemical structure looks similar to cholesterol)
Triterpenes are the heaviest of the three since they have 30 carbons and the others have 10 and 15 carbons respectively. Within the mushroom cell, triterpenes are converted into various metabolites including sterols, steroids, and saponins. They are produced via a pathway called the mevalonate pathway with a starting molecule called acetyl-coa. Animals have a very similar pathway that leads to cholesterol synthesis! This pathway in fungi also leads to ergosterol (a precursor to vitamin D2) which plays the same role that cholesterol plays in the human cell. It is a major component of the plasma cell membrane in fungi, important for membrane permeability.
Cytochrome p450 is important in gene expression and triterpenoid production. There is significantly more CYP450 during the transition from primordia to fruiting bodies, correlating with a higher triterpene content in the mushroom fruiting bodies. – developmental stage of fungal growth plays an important role in the regulation of secondary metabolite genes. (rep NP) (Schmidt-dannert, Schrader)
In the Human
Volatile compounds are very low molecular weight and cross easily through barriers and membranes. It is for this reason that essential oils are so readily absorbed through the skin and mucous membranes. Some volatile compounds can be neurotoxic for this reason, and some can be neuroprotective. There is research now exploring the role of octanol as an antiseizure agent. (Manjarrez-Marmolejo, chang, jahromi) Octanol reduced seizure induction and seizure discharges when it was applied directly to the epileptic focus in the somatosensory cortex. Additionally, it has been reported that administration of octanol significantly reduces the frequency and amplitude of epileptiform spikes, as well as the epileptic behavioral score induced by the administration of penicillin. (Manjarrez).
Some fungal sesquiterpenes have also been shown to inhibit TGF-b, decreasing kidney fibrosis in late stage kidney disease. Triterpenes are major compounds of interest in cancer research. Triterpenes have been shown to be directly cytotoxic to many cancer cell lines. (Rios, Grienke, Bhattarai, Ren, Jin, , Zhu) Triterpenes also have specific antiviral activity, inhibiting an enzyme, neuraminidase, which is important for viruses to be able to leave one cell to enter another. (Teplyakova, Gao) Triterpene compounds have been shown to be very beneficial in treatment of hypersensitivity reactions. Hypersensitivity reactions include allergy, asthma, dermatitis, and rhinitis. Triterpenes inhibit histamine release from mast cells – less histamine will result in less of a reaction. These can also be used in treatment of inflammatory reactions caused by insect stings and bites. (Rios)
Volatile compounds need to be extracted from fresh mushrooms and will escape into the atmosphere with heat. They are alcohol and fat soluble. Best to do a cold ethanol extraction for volatile compounds. 24 hours is sufficient.
Triterpenes will not volatilize and are also fat and alcohol soluble. There are terpenes within the cell, and so it is best to break the chitin cell wall first with a water decoction, before proceeding with ethanol to extract the triterpenes. A triple extraction method will be provided at the end of this post.
– Molecules that are long chains of lipid-carboxylic acid found in fats and oils and in cell membranes as a component of phospholipids and glycolipids –
In the Mushroom
Principal lipids in mushrooms are palmitic and linoleic acid. The fruiting body and pileus (cap) contains more linoleic acid and the stipe contains for oleic acid. The linoleic acid plays a role in fungal reproductive mechanisms. Trametes versicolor contains more short chain fatty acids – octanoic, decanoic and lauric acid. (Summer) Fungal membranes contain large quantities of free fatty acids, specifically glycerolipids and acylglycerols. These fatty acids occur in fungi as the major constituents of oil droplets suspended in mycelial and spore cytoplasm. They are also minor constituents of membranes and cell walls. Their primary function is storage material. Phophoglycerides are formed from a combination of fatty acids and are found primarily in the plasma membrane of cellular organelles, where they occur as complexes with proteins.
In the Human
Short chain fatty acids found in Trametes species modifies human fecal microbiota composition, increasing healthy bacteria – Bifidiobacteria and Lactobacillus while decreasing E.coli. (Yu) Short chain fatty acids also lower the intestinal pH, inhibiting growth of microbial pathogens (Plummer)
These fatty acid compounds also have antioxidant activities found to be as effective as alpha-tocopherol (Vit E) while also showing significant antimicrobial and anti-fungal activity. (Younis)
Fat and alcohol soluble
-The term ‘phenolic’ or ‘polyphenol’ can be defined chemically as a substance which possesses an aromatic ring bearing one or more hydroxy substituents, including functional derivatives (esters, methyl ethers, glycosides etc.)- Commonly known phenolic compounds include: bioflavonoids and proanthocyanidins
In the Mushroom
The phenolic compounds in mushrooms are secondary metabolites derived from intermediates of the shikimic acid pathway, the primary role of which is to provide the essential aromatic amino acids phenylananine, tyrosine and tryptophan. The intermediates of the shikimic acid pathway are precursors of aromatic compounds, including phenolic compounds. The biosynthesis of these compounds has demonstrated that they possess enzymes such as ammonia-lyases that convert phenalynine and tyrosine to cinnamic acids. These compounds represent the building blocks for pigments in mushrooms. The phenolic compound hispolon is an example of a yellow pigment in mushrooms. (Velisek)
In the Human
Phenolic compounds act as powerful antioxidants in the human organism. These compounds help to reduce oxidative stress through their own free radical scavenging activity as well as through stimulating the innate human antioxidant systems. (Geng) Phenolic compounds in mushrooms have also been shown to inhibit alpha-glucosidase in rats and significantly help with diabetic complications caused by this compound. A specific phenolic compound, hispolon, found in Phellinus species has been shown to have analgesic and anti-inflammatory effects as well as inhibits the growth of human cancer cells via the inhibition of the cytokine, TGF-beta. Hispolon also activates caspase, an important enzyme that induces cancer cell death. (Govindappa, Huang, Hong, Chang, Wu, Hsieh)
Ethanol or Water depending on how polar the phenolic compound is, best to do a triple extraction so you are sure to get them all.
The best way to get all of these compounds in one extract is to do a triple extraction method. The first part of the triple extraction is an overnight ethanol extraction. I use 95% ETOH and poor it over finely chopped/shredded fresh mushroom. Let this sit for 24-48 hours. Press the ETOH from the mushroom material and set aside (ETOH extract #1). Next, place the mushrooms from the original extraction into a crockpot or soup pot, cover with water and simmer for 2-12 hrs (The aqueous extract). Next, place these mushrooms and aqueous extract into a jar and leave the jar 1/3 empty. Fill the last 1/3 of the jar with the ETOH extract #1. Let sit (macerate) for a few weeks, shaking and loving daily. Press out mushrooms (the marc) from ETOH/Aqueous solvent (menstruum). Now you have your triple extraction – containing the volatile compounds, the polysaccharides, the triterpenes, phenolic compounds, and fatty acids.
Bhattarai G, Lee Y-H, Lee N-H, et al. Fomitoside-K from Fomitopsis nigra Induces Apoptosis of Human Oral Squamous Cell Carcinomas (YD-10B) via Mitochondrial Signaling Pathway. Biol Pharm Bull. 2012;35(10):1711-1719. doi:10.1248/bpb.12-00297.
Chang H, Sheu M, Yang C, et al. Analgesic Effects and the Mechanisms of Anti-Inflammation of Hispolon in Mice. 2011;2011. doi:10.1093/ecam/nep027.
Chang WP, Wu JJS, Shyu BC. Thalamic Modulation of Cingulate Seizure Activity Via the Regulation of Gap Junctions in Mice Thalamocingulate Slice. PLoS One. 2013;8(5). doi:10.1371/journal.pone.0062952.
Friedman M. Mushroom Polysaccharides : Chemistry and. 2016. doi:10.3390/foods5040080.
Gao L, Sun Y, Si J, et al. Cryptoporus volvatus extract inhibits influenza virus replication in vitro and in vivo. PLoS One. 2014;9(12). doi:10.1371/journal.pone.0113604.
Geng P, Siu KC, Wang Z, Wu JY. Antifatigue Functions and Mechanisms of Edible and Medicinal Mushrooms. Biomed Res Int. 2017;2017. doi:10.1155/2017/9648496.
Grienke U, Kaserer T, Pfluger F, et al. Accessing biological actions of Ganoderma secondary metabolites by in silico profiling. Phytochemistry. 2015;114:114-124. doi:10.1016/j.phytochem.2014.10.010.
Griffin, David H. (State University Of New York, U. Usa. Fungal Physiology. John Wiley And Sons, 1996.
Guggenheim AG, Wright KM, Zwickey HL. Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. Integr Med. 2014;13(1):32-44
Hong D, Park MINJU, Jang EUNH, Jung BOM, Kim NAMJ, Kim JHO. Hispolon as an inhibitor of TGF ‑ β ‑ induced epithelial ‑ mesenchymal transition in human epithelial cancer cells by co ‑ regulation of TGF ‑ β ‑ Snail / Twist axis. 2017:4866-4872. doi:10.3892/ol.2017.6789.
Hsieh M, Chien S, Chou Y, Chen C, Chen J, Chen M. Phytomedicine Hispolon from Phellinus linteus possesses mediate caspases activation and induces human nasopharyngeal carcinomas cells apoptosis. Eur J Integr Med. 2014;21(12):1746-1752. doi:10.1016/j.phymed.2014.07.013.
Huang G, Hsieh W, Chang H, Huang S, Lin Y, Kuo Y. r -Glucosidase and Aldose Reductase Inhibitory Activities from the Fruiting Body of Phellinus merrillii. 2011:5702-5706. doi:10.1021/jf2003943.
Jahromi SS, Wentlandt K, Piran S, Carlen PL. Anticonvulsant actions of gap junctional blockers in an in vitro seizure model. J Neurophysiol. 2002;88(4):1893. doi:10.1152/jn.00801.2001.
Jin X, Ruiz Beguerie J, Sze DM-Y, Chan GCF. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane database Syst Rev. 2016;4:CD007731. doi:10.1002/14651858.CD007731.pub3.
Manjarrez-Marmolejo J F-PJ. Gap Junction Blockers: An Overview of their Effects on Induced Seizures in Animal Models. Curr Neuropharmacol. 2016;14(7):759-771. doi:10.2174/1570159X14666160603115942.
Melappa G, Roshan A, Nithi C, Mohummed TS, – C, Poojari CC. Phytochemical analysis and in vitro antioxidant, antimicrobial, anti-inflammatory and cytotoxicity activities of wood rotting fungi, Trametes ochracea. Pharmacogn J. 2015;7(2):136-146. doi:10.5530/pj.2015.2.8.
Morath SU, Hung R, Bennett JW. Fungal volatile organic compounds: A review with emphasis on their biotechnological potential. Fungal Biol Rev. 2012;26(2-3):73-83. doi:10.1016/j.fbr.2012.07.001.
Plummer NT. Part 2: Treatments for Chronic Gastrointestinal Disease and Gut Dysbiosis. 2015;14(I):25-33.
Ren G, Liu XY, Zhu HK, Yang SZ, Fu CX. Evaluation of cytotoxic activities of some medicinal polypore fungi from China. Fitoterapia. 2006;77(5):408-410. doi:10.1016/j.fitote.2006.05.004.
Rep NP. Traversing the fungal terpenome. 2015;31(10):1449-1473. doi:10.1039/c4np00075g.Traversing.
Ríos JL. Effects of triterpenes on the immune system. J Ethnopharmacol. 2010;128(1):1-14 doi:10.1016/j.jep.2009.12.045.
Rösecke J, Pietsch M, König WA. Volatile constituents of wood-rotting basidiomycetes. Phytochemistry. 2000;54(8):747-750. doi:10.1016/S0031-9422(00)00138-2.
Schmidt-dannert C. Biosynthesis of Terpenoid Natural Products in Fungi. 2015;(November 2014):19-61. doi:10.1007/10.
SCHRADER, JENS. BIOTECHNOLOGY OF ISOPRENOIDS. SPRINGER INTERNATIONAL PU, 2016.
Shamtsyan M, Antontceva E, Panchenko A, Petrischev N. HYPERLIPIDEMIC AND HYPOCHOLESTEROLIC ACTION OF SUBMERGE CULTURED MUSHROOMS.
Sumner JL. The fatty acid composition of basidiomycetes. 2012;8643(1973). doi:10.1080/0028825X.1973.10430293.
Taborda CP, Janeiro R De. GLYCOCONJUGATES AND POLYSACCHARIDES OF FUNGAL CELL WALL AND ACTIVATION. 2008:195-208.
Teng F, Bito T, Takenaka S, Yabuta Y, Watanabe F. Vitamin B 12 [ c ‑ lactone], a Biologically Inactive Corrinoid Compound, Occurs in Cultured and Dried Lion ’ s Mane Mushroom ( Hericium erinaceus ) Fruiting Bodies. 2014. doi:10.1021/jf404463v.
Teplyakova T V., Psurtseva N V., Kosogova TA, Mazurkova NA, Khanin VA, Vlasenko VA. Antiviral Activity of Polyporoid Mushrooms (Higher Basidiomycetes) from Altai Mountains (Russia). Int J Med Mushrooms. 2012;14(1):37-45. doi:10.1615/IntJMedMushr.v14.i1.40.
Velíšek J, Cejpek K. Pigments of Higher Fungi : A Review. 2011;29(2):87-102.
Wu Q, Kang Y, Zhang H, Wang H, Liu Y, Wang J. Biochemical and Biophysical Research Communications The anticancer effects of hispolon on lung cancer cells. Biochem Biophys Res Commun. 2014;453(3):385-391. doi:10.1016/j.bbrc.2014.09.098.
Younis AM, Wu F-S, El Shikh HH. Antimicrobial Activity of Extracts of the Oyster Culinary Medicinal Mushroom Pleurotus ostreatus (Higher Basidiomycetes) and Identification of a New Antimicrobial Compound. Int J Med Mushrooms. 2015;17(6):579-590. doi:10.1615/IntJMedMushrooms.v17.i6.80.
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.
Zhu Q, Bang TH, Ohnuki K, Sawai T, Sawai K, Shimizu K. Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design. Sci Rep. 2015;5(AUGUST):13194. doi:10.1038/srep13194.
Medicinal Fungi complement the human system on a complexity of different levels. The awareness of mushrooms for medicinal use is most present in conversations around the immune system, yet there are further dialogues – in more recent research and in deeper exploration of ethno-mycological studies – that mushrooms support just about every system in the human body, not solely the immune system. This post is going to focus on mushrooms and movement. Specifically, how medicinal mushrooms support the human system through different anti-fatigue mechanisms allowing us to move better longer and with reduced risk of injury.
There are several theories of peripheral fatigue, and not surprisingly, many medicinal mushrooms support the bulk of them. Theories range from metabolic depletion; ATP and creatine-phosphate specifically, lactic acid accumulation, oxidative stress with depletion of endogenous anti-oxidant capabilities, muscle and liver glycogen depletion, tissue damage, and central/psychological factors.
Lactic Acid Accumulation
Let’s first focus on lactic acid accumulation. The accumulation of lactic acid during exercise will inhibit energy metabolism and reduce muscular endurance, resulting in fatigue. (The accumulation of lactate can interfere with nerve impulse and therefore muscle contraction) The theory goes, that if lactic acid accumulation can be controlled, then fatigue wont set in as quickly. Medicinal mushrooms such as Lion’s Mane, Hericium erinaceus, Reishi, Ganoderma spp. and Cordyceps spp.
all enhance the rate of lactic acid clearance during exercise or in the case of Cordyceps, can even inhibit production of lactic acid.1,5,7 The polysaccharides in H. erinaceus had a positive effect on the swimming time of mice, significantly increasing their exercise tolerance in a forced swimming model. Ganoderma spp., Tremella spp. and Cordyceps spp. have been shown to stimulate the enzyme lactic acid dehydrogenase (LDH). The increase in LDH activity helps to increase ATP for exercise under anaerobic conditions as well as accelerate removal of lactic acid. From this information, we can postulate that when we have these mushroom extracts in our systems during exercise, we may benefit from a decrease in lactic acid accumulation, and therefore improve our endurance.
It is no surprise that Cordyceps has been found to improve exercise tolerance. This is of course, how this organism has been used for centuries. The Nepalese people observed live-stock consuming Cordyceps and saw how it increased their sexual vitality and general stamina. They began to consume them as the other animals were, and found that it increased their own vitality as well – increasing stamina, endurance, and treating impotence.15
Intense use of skeletal muscle during exercise leads to oxidative stress. Of course the human system has its own antioxidant system built in, but this system can be weakened through excessive exercise leading to more oxidative stress. Medicinal mushrooms such as Ganoderma lucidum, Tremella spp., Cordyceps spp. and Fomitopsis pinicola all help to mitigate fatigue by supporting the free radical scavenging ability within the human antioxidant system.4,6,11 These mushrooms support superoxide dismutase, glutathione reductase, and catalase; all endogenous enzymes involved in innate antioxidant functions. In a human double-blind placebo trial that assessed the oxidative stress biomarkers in athletes supplementing with Cordyceps and Ganoderma, the researchers found that after 3 months of supplementation with 1335mg Cordyceps extract per day and 1170mg Ganoderma extract per day, the athletes had significantly more free radical scavenging activity after a race than the placebo group.17
One study that explored Ganoderma tsugae, a mushroom very closely related to our local Ganoderma oregonense, found significant liver protection against exhaustive exercise-induced liver injury in rats.10 “The results concluded that G. tsugae could increase the running time to exhaustion in animals, decrease lipid peroxidation and protect against hepatic apoptosis after exhaustive exercise.” Basically, G. tsugae has protective effects on the liver that can improve exercise performance.
Ganoderma spp. and Cordyceps spp. contain the nucleoside adenosine.17 Adenosine is a regulator of skeletal muscle blood flow. The role of adenosine in exercise is vascular smooth muscle relaxation, contributing to the local vasodilation which accompanies muscle contractions. Adenosine contributes around 14-29% to vasodilation in humans especially during higher frequency contractions, like during exercise. Increased 40% in exercise lasting longer than 5 minutes.2
Ganoderma applanatumalso increases endothelial nitric oxide synthase. This also has a dialing effect on the endothelial smooth muscle in our blood vessels, increasing blood flow to skeletal muscle.14
This is the first post where I have discussed mushrooms that do not necessarily grow here in the PNW. I feel confident that our local Ganoderma species would have analogous interactions with our biochemistry as Ganoderma lucidum. I also think that the west coast Hericiumspecies are analogous with Hericium erinaceus. Cordyceps are more common in the Himalayas and South America and worth investing in for personal stamina experimentation. In my experience, they are extremely powerful. We are however, extremely fortunate to have abundance of Fomitopsis pinicola, which has a beautiful relationship with our innate free-radical scavenging systems and I would propose more use for this mushroom in relation to physical exercise.
Making medicine to support you through exercise
Beet Juice Matcha Latte
Why Beets and Matcha?
Beetroot juice increases blood flow and increases efficiency of mitochondrial respiration and oxidative phosphorylation9
In a study evaluating the anti-fatigue effects of Epigallocatechin-3-gallate, a polyphenolic compound in green tea, the researchers concluded that EGCG significantly prolonged exhaustive swimming time of mice.8 In another study done on male sprinters, green tea extract supplementation prevented oxidative stress.12 The polyphenolic compounds in green tea were also found to significantly protect rats from fatigue, inflammation and tissue damage induced by acute exhaustive exercise.13
Geng P, Siu KC, Wang Z, Wu JY. Antifatigue Functions and Mechanisms of Edible and Medicinal Mushrooms. Biomed Res Int. 2017;2017. doi:10.1155/2017/9648496.
Ballard HJ. Invited Review ATP and adenosine in the regulation of skeletal muscle blood flow during exercise. Sheng Li Xue Bao. 2014;66(1):67-78. doi:10.13294/j.aps.2014.0009.
Mateo DC, Pazzi F, Muñoz FJD, et al. Ganoderma lucidum improves physical fitness in women with fibromyalgia . Nutr Hosp. 2015;32(5):2126-2135. doi:10.3305/nh.2015.32.5.9601.
Zhonghui Z, Xiaowei Z, Fang F. Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice. Saudi J Biol Sci. 2014;21(2):119-123. doi:10.1016/j.sjbs.2013.04.004.
Song J, Wang Y, Teng M, et al. Studies on the antifatigue activities of Cordyceps militaris fruit body extract in mouse model. Evidence-based Complement Altern Med. 2015;2015. doi:10.1155/2015/174616.
Hao L, Sheng Z, Lu J, Tao R, Jia S. Characterization and antioxidant activities of extracellular and intracellular polysaccharides from Fomitopsis pinicola. Carbohydr Polym. 2016;141:54-59. doi:10.1016/j.carbpol.2015.11.048.
Liu J, Du C, Wang Y, Yu Z. Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus. Exp Ther Med. 2015;9(2):483-487. doi:10.3892/etm.2014.2139.
Teng Y, Wu D. Anti-fatigue effect of green tea polyphenols (-)-Epigallocatechin-3-Gallate (EGCG). Pharmacogn Mag. 2017;13(50):326. doi:10.4103/0973-1296.204546.
Domínguez R, Cuenca E, Maté-Muñoz JL, et al. Effects of beetroot juice supplementation on cardiorespiratory endurance in athletes. A systematic review. Nutrients. 2017;9(1):1-18. doi:10.3390/nu9010043.
Huang CC, Huang WC, Yang SC, Chan CC, Lin WT. Ganoderma tsugae hepatoprotection against exhaustive exercise-induced liver injury in rats. Molecules. 2013;18(2):1741-1754. doi:10.3390/molecules18021741.
Reis FS, Pereira E, Barros L, Sousa MJ, Martins A, Ferreira ICFR. Biomolecule profiles in inedible wild mushrooms with antioxidant value. Molecules. 2011;16(6):4328-4338. doi:10.3390/molecules16064328.
Jówko E, Długołęcka B, Makaruk B, Cieśliński I. The effect of green tea extract supplementation on exercise-induced oxidative stress parameters in male sprinters. Eur J Nutr. 2015;54(5):783-791. doi:10.1007/s00394-014-0757-1.
Liu L, Wu X, Zhang B, et al. Protective effects of tea polyphenols on exhaustive exercise-induced fatigue, inflammation and tissue damage. Food Nutr Res. 2017;61(1):1333390. doi:10.1080/16546628.2017.1333390.
Acharya K, Yonzone P, Rai M, Acharya R. Antioxidant and nitric oxide synthase activation properties of Ganoderma applanatum. Indian J Exp Biol. 2005;43(10):926-929.
Panda A, Swain K. Traditional uses and medicinal potential of Cordyceps sinensis of Sikkim. J Ayurveda Integr Med. 2011;2(1):9. doi:10.4103/0975-9476.78183.
Singh M, Tulsawani R, Koganti P, Chauhan A, Manickam M, Misra K. Cordyceps sinensis increases hypoxia tolerance by inducing heme oxygenase-1 and metallothionein via Nrf2 activation in human lung epithelial cells. Biomed Res Int. 2013;2013:1-13. doi:10.1155/2013/569206.
Rossi P, Buonocore D, Altobelli E, et al. Improving training condition assessment in endurance cyclists: Effects of ganoderma lucidum and ophiocordyceps sinensis dietary supplementation. Evidence-based Complement Altern Med. 2014;2014. doi:10.1155/2014/979613.
Winter; Traditionally a time of sleeping, eating, and burrowing. Though, we no longer live with the seasons in our society, so consequently, winter has become a time, like all the other times, one of business and stress. This resistance to succumb to the slow, dark pace of winter can result in a manifestation of disease. We are fortunate during this time to have the plants and fungi as our allies.
Love the polypore perennial mushrooms for allowing harvest throughout all seasons.
“Without leaves, without buds, without flowers, yet from fruit; as food, as tonic, as medicine: the entire creation is precious.” – A poem found in an ancient Egyptian temple
Let us neither forget nor ignore this preciousness during this season.
Polypore Mushrooms endure great stress. They are some of the most weathered beings out there. As I sit cozy inside, the Fomitopsis’ the Trametes’ and Ganodermas of the forest stand the wind, the rain, the snow, the cold, the warmth, yet they continue to grow, gaining more resistance as the weathers abound.
I was recently reading about this therapy of ‘Grounding’ – The idea that the electrical currents from the earth can improve our sleep, anxiety, inflammation, and accelerate healing time post injury. As our deep fascial network provides a mycelium like sock over our musculature, electrical currents run through passing information throughout. Each muscle its own knoll, and valleys and ravines lay in between. These waves move in amongst and throughout it all delivering signals around. When there is a blockage in this fascial network, these signals do not move as quickly. A blockage can be formed from events like tight muscles, dehydration, inflammation – knots can form from lack of stretching and water intake, fascia will bind to muscle and skin, making it difficult for information to pass. Electrical pulses stimulate the growth of mycelium, and very well do they hasten our own healing. The electrical pulse of the earth in direct collaboration with our own mycelial-like fascial network can improve our own response to stress and inflammation. Mycelia work as a network of communication for the flora of the forest, as our fascia and neurons do for our own internal terrain. Maybe this connection is the doctrine of signatures that explains a way that mushrooms work as adaptogens – how they help our bodies adapt to stress – or decrease the blockages so information can move through without so many obstacles, in turn increasing our own vitality, or Qi.
(These pictures look strangely similar to me, I don’t now if everyone will feel that way)
Polypore Mushrooms and the Stress Response
This idea about the fascia and blockage of our information network is just me postulating about the doctrine of signatures relating mycelium to fascia. There is much information regarding Medicinal Mushrooms being beneficial for what can be debilitating consequences of a prolonged stress response. This is a good time to grasp this knowledge, seeing that it is the holiday season and many of us have time off from stressful lives at school and work, and then are hit with the stress of the holidays. The response to stress is, like most of our bodily processes, beautiful, perfect, and a negative feedback loop, not meant to be constant. Throughout history of humanity, the stress response is critical to acute stressors, and up until recently in civilization this idea of chronic stress did not exist. The systemic response to stress is the HPA axis. This is the Hypothalamus-pituitary-adrenal axis. When a stressor occurs, like being chased by a bear, or having to take an exam, the hypothalamus releases corticotropin releasing hormone, signaling the pituitary to release adrenal corticotropin releasing hormone and then the adrenals release catecholamines, and corticosteroids such as cortisol. The cortisol then acts on the hypothalamus in a negative feedback system, turning off the production so that no more cortisol will be released. When this stress turns chronic, the negative feedback system stops working so well – the adrenals become fatigued. This can then lead to fatigue, inability to fall asleep and/or stay asleep, immune system suppression, weight gain, low libido, etc.
Adaptogens are a class of herbs and fungi which facilitate the body in adapting to this chronic stress. Ideally we would be able to stop the major cause of stress and would not need the adaptogens, but that isn’t always an option. Adaptogens can be both beneficial and detrimental to ones health, depending on the ones we choose. A more stimulating adaptogen like Rhodiola rosea or Panax ginseng can help in the time of stress but then, consequently, leave you feeling even more burnt out. Medicinal mushrooms are considered to be gentle and safe, and I have yet to hear of someone experiencing burnout from taking them. Though, they do not tend to work directly with the HPA axis, so some would not even consider them adaptogens. Other than one article¹ reporting positive anxiolytic effects in mice, using Royal Sun medicinal mushroom, Agaricus brasiliensis, I have not been able to find any research regarding medicinal mushrooms and the HPA axis specifically, but rather an abundance of research regarding the mushrooms and the repercussions of chronic stress; this being their immunomodulating, hepatoprotective, antihistamine, weight stabilizing, anxiolytic, aphrodisiac and anti-tumor properties.
The Triterpenes, or secondary metabolites, have been studied the most in this regard. The spores and crust of the polypore mushrooms have the highest triterpene content, and these are best extracted using methanol, ethanol, acetone, or oil (You will see in the recipe below, that there is coconut oil added to the syrup for this reason). A comprehensive review² of the biological activities of Ganoderma ssp. triterpenes concluded numerous actions that indirectly help the body to adapt to stress. Allergies and viruses are more active when our body is under stress, and the Ganoderma triterpenes have been found to have potent activity against herpes simplex virus and inhibit histamine release. Lanostane triterpenes, (the triterpenes found in Ganoderma spp.) Ganoderic acid B and C both have histamine inhibitory effects.³ In regards to body fat, Ganoderma triterpenes were found to significantly reduce triglyceride accumulation by 72%, as well as inhibiting HMG-COA reductase (the key regulatory enzyme in cholesterol production). Under stress, it also becomes difficult to think clearly and the Ganoderma triterpenes have anti-cholinesterase activity. Less degradation of the neurotransmitter Acetylcholine can improve cognitive functioning, and some anticholinesterase drugs are used to treat Alzheimer’s disease. (Rosmarinus officinalis and Salvia miltiorrhiza both have anticholinesterase activity as well – I’m sure you have heard of Rosemary enhancing memory. Also, under chronic stress inflammation may be more prevalent. Macrophages are one of the critical immune cells in the regulation of inflammatory responses. Activated macrophages secrete a number of different inflammatory mediators. When there is an excessive production of these mediators, inflammatory disease is exacerbated. Lanostane triterpenes can help prevent and treat inflammatory disease by inhibiting production of inflammatory cytokines.4Ganoderma applanatum, Ganoderma oregonense and Fomitopsis pinicola all contain these lanostane triterpenes.
Mushrooms, like people, are more than just a bunch of different molecules. They contain their own energy and this is one of strength and endurance. We don’t need to know about the chemicals they contain to know that they are grounding beings of great vigor. Simply observing this, and their way of being throughout the seasons, gives us enough information that they are superb and precious medicine, and a medicine that can be of great importance during times of stress.
Recipe for the Season – A syrup to help with holiday stress and viral defense
Elderberry and Fungi Syrup
½ C Elderberries
6 Ganoderma slices
¼ C Chaga mushroom pieces
1 Tbs Licorice root, chopped
1 Tbs Ginger (Dried and chopped is fine, but fresh juice will have stronger antiviral action)
1/3 C coconut oil
2 1/4 C water
Put all ingredients, except for honey and ginger juice, in a pot and heat until it comes to a boil
Bring down to a simmer
Mash up with potato masher every once in a while
When water has reduced by half (about 45 min), decant liquid from plant and mushroom material
You can let it cool down a bit, put it all in a cheese cloth and squeeze as hard as you can
Mix raw honey with ginger juice and oil-water extract so they are equal parts (Honey:Extract+Ginger juice, 1:1)
With a hand held emulsifier, hand blender or any other kind of blender, emulsify the mixture. The purpose of this is so that there isn’t a layer of oil sitting on top of your syrup. Also, doing this emulsification step creates a creamy delicious consistency.
Store in little glass jar
Put on Oatmeal, Pancakes, Waffles, or just take it by itself!
Zhang, Chunjing, Xiulan Gao, Yan Sun, Xiaojie Sun, Yanmin Wu, Ying Liu, Haitao Yu, and Guangcheng Cui. “Anxiolytic Effects of Royal Sun Medicinal Mushroom, Agaricus Brasiliensis (Higher Basidiomycetes) on Ischemia-Induced Anxiety in Rats.” International Journal of Medicinal Mushrooms Int J Med Mushrooms 17.1 (2015): 1-10. Web.
Xia, Qing, Huazheng Zhang, Xuefei Sun, Haijuan Zhao, Lingfang Wu, Dan Zhu, Guanghui Yang, Yanyan Shao, Xiaoxue Zhang, Xin Mao, Lanzhen Zhang, and Gaimei She. “A Comprehensive Review of the Structure Elucidation and Biological Activity of Triterpenoids from Ganoderma Spp.” Molecules 19.11 (2014): 17478-7535. Web.
Ríos, José-Luis. “Effects of Triterpenes on the Immune System.” Journal of Ethnopharmacology 128.1 (2010): 1-14. Web.
Dudhgaonkar, Shailesh, Anita Thyagarajan, and Daniel Sliva. “Suppression of the Inflammatory Response by Triterpenes Isolated from the Mushroom Ganoderma Lucidum.” International Immunopharmacology 9.11 (2009): 1272-280. Web.
Disclaimer: The information I provide on this blog isn’t intended to treat or diagnose any disease, just information from published research, read by me and written to you. You can decide what to do with it.
The 16th century alchemist, Paracelsus, explained,”[Alchemy] is like unto death, which separates the eternal from the mortal, so that it should properly be known as the death of things.” I hadn’t thought much about alchemy and death before reading this quote, but had always thought about mushrooms as the alchemists of nature – assisting in the dying process, breaking down the mortal and transforming the eternal to birth new life – and so with the noticing of the fungi-death connection and mushroom-alchemy connection, it would make sense that “alchemy is like unto death”. I am not talking about turning lead into gold, but a different kind of alchemy. In the alchemy that is of interest to me is assisting in the transformation of plants and mushrooms. This herbal alchemy uncovers secrets in the vegetable and fungi realm through distillations and calcinations, separating the eternal plant soul and spirit, from the mortem or mortal body. There is much to learn from mushrooms about the dying process, and what I have found, through a cocktail of my own experiences and readings about the fungi used in the Chinese Materia Medica, is that mushrooms are strong medicine, physically and spiritually, throughout any process in experiencing loss. I think they can be an important medicine and ally for people during times of grief, pre and post death.
The mushroom-like herb that is most often used throughout the dying process is Indian pipe, Monotropa uniflora. Though, this is neither a mushroom nor a a typical photosynthesizing plant. M. uniflora is a saprophyte, benefiting off of an already established relationship between a plant and fungi. This ghostly plant has a history of use not only as an ‘antipsychotic’ but also used throughout bereavement, both for the person who is themselves dying and for those who are grieving their loss. My love and curiosity about this saprophytic plant has had a part in instigating my wanderings into the realm of fungi and mortality.
This mushroom medicine is of a different kind than what I usually write about. This is the kind of medicine that goes deeper than chemical processes, this mushroom medicine reaches your spirit. It is true, that in times of grief your immune system will be down and your adrenals will probably need support, and so the mushrooms will be helpful in keeping your body systems strong, but they will also keep your spirit strong. In Chinese medicine the Reishi mushroom, Ganoderma lucidum, is known to nourish the Shen,or the Spirit, which resides in the heart.
In fact, the spagyric of the Oregon Reishi, G. oregonense is the most immediately uplifting medicine I have yet to try. I talk about the experience on the specific post titled, “Ganoderma oregonense“. The mushroom medicine can lighten the heavy, grieving heart, and be uplifting in times of bereavement. It has been my experience that it is not only the Reishi mushrooms that can be an ally when the spirit is vulnerable, but all polypore mushrooms that I have thus far talked about throughout this blog. The mushroom’s mycelial network reminds us too of the importance of community throughout the dying process, the importance of reaching out, and getting permission to receive nourishment through our connections.
Recipe to Nourish the Spirit
This Kichri is nourishing to body and spirit, grounding, sustaining, and easy to make.
Things that are helpful to have: A crockpot
First, make the broth:
Place a handful of polypore mushrooms; Oregon Reishi, Artist’s Conk, Red Belted Polypore, Turkey tail.. (slices or whole) into Crockpot and fill with water (If you do not have a crockpot, simmer on your stove top on low heat)
Add chopped onion and garlic
Put the lid on and place on low
Let simmer for at least 2 hours (it is easiest to throw it in the pot and let simmer over night or throughout the day)
Strain out Mushrooms from the broth (these mushrooms are too woody to eat)
If you are into Bone Broth, bones make a delicious and nutritious addition
41/2 Cups Polypore Broth
1 Cup rice (any kind, I prefer brown, but do what you like)
1 Cup Mung Beans, uncooked
1 Sweet potato, chopped
1 C Nettles, dried or fresh
1.5 Tbs Ghee or Coconut oil
1 Tbs Garam Masala
Mix all ingredients in a crockpot or on stovetop
Bring to a boil, and then down to a simmer for about 2 hours. If you use a crockpot, you can have it on low throughout the day and come home to a nice hot meal.
Each process of work I engage in with the fungal kingdom continues to remind me of how similar we humans are to our fungal allies. Thus far, on this blog I have brought up research that I have collected on the various mushrooms, and barely touched on the different levels of medicinal preparations that I have been experimenting with. Most recently, I have been experimenting with polypore distillations.
This magnificent mushroom was collected early in the day, chopped, and then vitamixed (high speed blended into tiny fibers). After the body of the mushroom was processed into the smallest pieces possible, it was added to a 2L flask.
Steam distillation begins.
considering the limited information on the volatiles of G. applanatum, I was skeptical if there would be any oil collected at the end of this process. There was one paper I found in the journal of Essential Oil Research that tested for the essential oils of G. applanatum. The paper, “Volatile Metabolites from the Wood Inhabiting Fungi Bjerkandera adusta, Ganoderma applanatum, and stereum hirsutum” by Ziegenbein et al. found 22 volatile compounds that could could be identified, with R-(-)-1-octen-3-ol (Octanol) and phenylacetaldehyde being the major constituents of the oil. Other constituents found in amounts between 5-10% are (E)-2-octenal, (E,E) 2,4-decadienal, 2-nonenal and 5 ethyl cyclopentene-1-carbaldehyde. This is the first time that 5 ethyl-cyclopentene-e-carbaldehyde has been found as a fungal metabolite.
Octanol, also known as mushroom alcohol, is a chemical that attracts biting insects, like mosquitos. It can also be found in human breath and sweat. Maybe this is why the mosquitos love me so much…you could probably make a trap using the volatiles, put a bowl out with the hydrosol or a little oil and the mosquitos will go to that instead of to you. I would suggest not spraying yourself down with the hydrosol before walking through the woods. Octanol is found in many edible mushrooms and also Lemon Balm, Melissa officinalis. There is also small mention of it’s use in perfumery. In my experience with smelling the volatiles from this mushroom the scent is reminiscent of spicy, yet sweet decaying earth.( A hard to find smell in the world of perfumery) There is also research being done on using octanol to treat involuntary tremor disorders.
Phenylacetaldehyde is found abundantly in nature, it is a derivative of the amino acid, phenylalanine. This can be found in chocolate, flowers, and certain insect pheromones. It has also been used to flavor cigarettes and added to fragrances to add a grassy-rose like flavor.
(E) 2-octenal is used as a flavoring agent in food industry, said to have a nutty flavor, and is mostly found in fungi and lamb. Also, one of the major constituents in the stink bug stench!
(E,E) 2,4-decadienal is an aromatic substance found in butter and cooked beef. Said to have a deep fat, brothy flavor and smell. When distilling mushrooms, the entire room usually ends up smelling like cooked steak…
2-nonenal is an important aroma component in aged beer, and according to wikipedia the smell that comes along with the aging of humans.
After about an our of distillations, the fumes filled the air of my house, and my eyelids felt like bricks. complete exhaustion came over me and I napped for most of the time the distillate trickled through. This has been the strongest sedating effect I have felt from any substance I have encountered. It felt painful to stay awake. I suppose there is implication for the hydrosol to be used as a strong sedative. Since then, I have sprayed the hydrosol throughout my home before bed, and the sedating effect is still there. Ganoderma species have a history of use as a sedative, so this was no surprise.
After 2 hours there was a build up of fatty emulsion in the condenser and it slowly fell into the oil separator.
Hours went by, and the thick white substance continued to build up in the condenser. After turning the water off, the build up in the condenser fell in to the oil separator. The cold water running through the condenser was keeping it in a more solid form, and when the condenser warmed it softened and fell through. I thought it would potentially liquify at room temperature, but it stayed as a substance the consistency of lard. This smelled extremely aromatic; Decaying forest with coinciding notes of sweet and pungent.
I ended up collecting 20 oz of hydrosol and about a teaspoon of the lard-like substance.
I had a taste of the water left over in the boiling flask, strongly infused with the water soluble components of the mushroom, and it seemed to be the antidote to the sedation. It awoke me in a flash. Mushroom medicine is amphoteric medicine. If your immune system is suppressed the mushroom medicine will stimulate it, if it is overstimulated, the mushrooms will suppress it. This is the same with the energizing and sedating qualities of the Ganoderma sp. This experience is suggestive that I have separated these two qualities.
If anyone has any interest in working with this hydrosol in perfumery let me know, I am happy to provide it, as I know it is not easy to find.
The soul/volatile sulfur of G. applanatum is substantial. It is comforting, strong, balancing and grounding. A supportive and tenacious ally.
To read more about mushrooms and alchemy check out this beautiful website: Alchemycology.com
Where there is Birch, there is F. fomentarius. North-Eastern United States, Alaska, Northern Mainland Europe. Found on Hardwoods.
There is usually only one or two fruiting bodies found per tree. It is a perennial, parasitic mushroom. Each layer of tubing represents a new year of growth. The thin crust is striped with various shades of grey, while the flesh is dark golden-brown, and the pore surface is pale grey to white. The flesh of the fruiting body is also known as the trauma layer. It is this trauma layer that is used as a natural gauze, tinder, and amadou felt.
Spore print – pale yellow
Amadou, derived from a Northern French dialect, meaning “amorous”, or “inflames life”. This meaning is exemplified in the mushrooms historical use as tinder. This word also translates to the english word, spunk, meaning courage, bravery or determination, originally meant spark. (Spunk is a combination of spark and funk). Interestingly, the fungal essence is used for the burnt out artist, to help them get their spark back.
A 5000 year old Iceman, Otzi, was found with this polypore. In 1991 hikers found his preserved remains in a glacier in the Otzal Alps between Austria and Italy. It is thought that he was carrying this mushroom to preserve fire, use as insect repellent, and as his first aid kit.
The name, Fomes fomentarius means, “to use as tinder”. It is extremely flammable, but has a nice slow burn, perfect for long travels through the mountains. Additionally, and a perk for the insect-loved traveler, the smoke produced by the burning of this mushroom works as an excellent insect repellent. In addition to flame and insect deterrent, this mushroom is a powerful hemostat.
There is documentation of Hippocrates using F. fomentarius as a styptic in the fifth century BC. Also used as a styptic by surgeons, barbers and dentists, giving it the name “agaric of the surgeons”. There is also note of the Okanagan-Olville native Americans using this as a styptic, a wound dressing, and a cauterizing agent. They would place a piece of the softened amadou layer over the affected area and ignite. This amadou layer was also used as a wound dressing and styptic throughout Europe. In a German speaking Alpine area in Europe, where this mushroom was called Wundschwamm, F. fomentarius was sold in pharmacies in the form of styptic bandages. While carving the mushroom’s crust off to expose this styptic layer of amadou, I sliced my finger with a serrated knife and there was heavy bleeding. I quickly wrapped a piece of the amadou around my finger. My finger stopped bleeding within minutes, and the amadou stayed on my finger as a nice bandage.
This mushroom was also used in ritual smoking ceremonies, in Germany and Austria, and by the Khanty people in West Siberia. They would burn the fruiting bodies to obtain smoke when a person died. The smoke would burn as to avoid any influence of the deceased on the living. This smoke has also been used similar to moxibustion. The ignited mushroom is placed over different parts of the body to warm the meridians, helping with the movement of blood and qi.
Currently studied as a treatment for esophagus, gastric and uterine carcinoma. Recent research shows distinct antibiotic activity against Bacillus subtillis and staphylococcus aureus with antifungal activity against Aspergillus flavus.
Also, anti-inflammatory and analgesic activities have been documented.
How to make the Amadou
Sharp serrated carving knife
Hammer, ideally wide headed, like a Leatherman’s hammer
Washing Soda Solution (sodium carbonate)
Cut off the crust of the mushroom
This is done carefully with a sharp knife, serrated works well. You want to be careful here to not cut off too much of the trauma layer.
Cut the off the tubes*
This is done by making deep cuts in the tubes and then cracking them apart, and peeling them away from the trauma layer, careful to not peel too much of the trauma layer off with them. Remaining tubes can be cut away with a knife.
3. Soak trauma layer over night to a week in washing soda solution, or boil for at least 20 minutes
Pound damp trauma layer
5. Soak again, pound again, and repeat until desired thickness reached.
6. Let the amadou felt (trauma layer) dry out, and use, as you like!
* Don’t throw away the mushroom parts that have been removed from the trauma layer. Simmer these in water and drink as an immune boosting tea, or use the tubes as a candlewick.
Mycophobia of the West will only hurt us in the end. When you tell someone you are going mushroom hunting, a common reaction is, “Be careful!” This may even be a more common exclamation to someone going mushroom hunting, than someone going out animal hunting with a gun. This fear of the mushrooms is valid in some cases, as there are “deadly” mushrooms out there, but it has created a culture that is afraid to use mushrooms for medicine, and this leads to a lack of much needed research.
In Eastern countries, mushrooms have been prized as food and medicine for thousands of years. These are also countries that have emphasis on preventative medicine built into their culture. The saying goes, “Taking medicine when you are already sick is like digging a well when you are already thirsty.” This is the antithesis of the West’s approach to disease. Most research of the medicinal value of the mushrooms is coming from Asian countries and although there is a crossover in species between geographic location, there is little research on the medicinal polypores of the West. Getting ready to teach a class and collecting information about medicinal mushrooms local to the Pacific Northwest, I am disheartened by the lack of research being done in the United States. And the research that is done elsewhere, in Russia, Eastern Europe, and Asia is not being properly relayed to the public in the U.S. Consequently, most people are completely unaware of these powerful medicinals. Being that the US culture is one of chronic stress and synthesized consumables (food-like substances), these mushrooms are our greatest allies.
More people are taking Reishi and Chaga mushrooms these days, and for good reason, but neither of these mushrooms are found very close to where these people are living. For example, people will buy Reishi and Chaga mushrooms at a store, yet they will ignore the polypores in their local forest. One reason the local medicinal mushrooms are so powerful as medicine is because they have the secondary metabolites to fight off the bacteria, fungi, and viruses that threaten the animals in the same area. The Red Belted Polypore, an underutilized and very common polypore, grows in the dankest of places, exposed to many pathogenic microbiota. This same mushroom found in Europe will show similarities in polysaccharide and triterpene content, but it is my thought that the secondary metabolites specific to certain bacteria and viruses will be different. Like two humans that grow up in different cities; One human will have been exposed to certain pathogens and possibly built up immunity to them. Alternatively, a human in the other city is exposed to different pathogens, and will not have built up immunity to the pathogens exposed to the first human. For this reason, it could be true that using the medicinal mushrooms that grow in your region, rather than using a mushroom grown on sorghum in a lab and/or in a far away country, could have a medicinal advantage.
It is my hope that through sharing well researched information on this blog, that there will be a little less mycophobia in the world, and people will start to see the fungi and plants as allies.