Active Compounds in Medicinal Mushrooms
There’s a lot of different mushroom supplements to choose from and all claim to be directed for different uses. For example, many supplements contain a variety of different mushroom species in one capsule or tincture. Their aim depends on the different species present. All species of medicinal mushrooms have active constituents that work with your body in order to achieve some medicinal benefits. Active constituents in fungi or plants are simply the different chemicals that have a medicinal effect on the body. Some common but powerful medicinal mushrooms being sold in the supplement industry right now include Reishi, Chaga, Lion’s Mane, Turkey Tail, and Cordyceps.
The therapeutic properties of mushrooms result from specific active constituents. These consist mainly of “polysaccharides (in particular beta-d-glucans, polysaccharopeptides (PSP), polysaccharide proteins, and proteins. Furthermore, other bioactive substances, including triterpenes, lipids, and phenols, have been identified and characterized in mushrooms with proven medicinal properties.” (1)
Reishi (Ganoderma lucidum)
Reishi mushroom is a true gem of nature. It has a rich cultural history in Traditional Chinese medicine, being used to promote longevity, increase intellectual capacity, and for memory enhancement. In China, it’s even known as the mushroom of immortality and divine power. In the west, it’s widely used for its anti-inflammatory, immune modulating and liver regenerating properties. Reishi is a species complex, meaning it encompasses several fungal species of the genus Ganoderma. They all look similar but don’t all possess the same therapeutic values as the specific species Ganoderma lucidum. Numerous authors have shown that the most prominent pharmacologically active constituents of G. lucidum can be broadly grouped as triterpenoids or polysaccharides.
Most mushrooms are 90% water by weight. For G. lucidum, the remaining 10% consists of 26–28% carbohydrate, 3–5% crude fat, 59% crude fiber, and 7–8% crude protein. Ganoderic acid is a part of that 10% and it is the most abundant triterpenic acid found in G. lucidum, showing significant anti-cancer effects in both in vivo studies (taken place in a living organism) as well as in vitro studies. (performed in test tube or culture)
A 2009 study conducted by the Cancer Research Laboratory of Indianapolis has shown that the triterpenes of G. lucidum significantly lowered inflammation in macrophage cells, therefore slowing down TNF-a (tumor necrosis factor) production. TNF-a and inflammatory cytokines have both been shown to promote carcinogenesis which is the initiation of cancer within the body.
Cytokines are defined as regulators of host responses, in this case to inflammation.
Some act to make diseases worse by increasing inflammation and these types are specifically referred to as inflammatory cytokines. In short, the study states that “administration of G. lucidum triterpene extract suppressed inflammatory cytokine secretion in macrophage cells thus decreasing the level of inflammation and in vivo experiments clearly demonstrated that GLT also inhibited the production of TNF-alpha”
In 2011, a study by the Amala Cancer Research Center in India showed that triterpenes extracted from G. lucidum have anti-oxidative properties in vitro and can reduce oxidative damage by directly scavenging free radicals generated in the cell. In addition, administration of triterpenes to mice increased the activities of antioxidant enzymes and reduced radiation-induced oxidative DNA damage in mice. The ability of triterpenes to search for and collect free radicals as well as enhance the natural antioxidant enzymes present within the body indicates that triterpenes are an ultra-efficient anti-oxidant. That study went on to say that in contrast to triterpenes, numerous other studies have proven that polysaccharides have an anticancer effect due to enhancing the host’s immune system rather than through direct cytotoxic effects.
Extractions using ethanol have been reported to be the easiest approach to maintain the activity of the triterpene extracts and to scale up its production. Triterpenes are usually extracted using organic solvents ethanol followed by different separation methods. In conclusion, G. lucidum could be a promising approach for cancer prevention and cancer treatment based on the available data we’ve obtained from both in vitro and in vivo studies.
Chaga (Inonotus obliquus)
Chaga is known as a mushroom containing an antioxidant powerhouse however it’s not really a mushroom at all. This species is actually just a hardened mass of mycelium called sclerotium that looks like burnt charcoal. It grows by using a very vibrant tree as its host for nutrients. Its traditional use lies mostly from Russian folk medicine where it's used commonly as a general tonic. Medicinal use dates all the way back to the 16th century but like most mushrooms, it’s only just now being utilized in the states.
It’s very well known in the states for its anti-inflammatory, anti-bacterial, antioxidant content, and anti-tumor properties. It contains beta-d-glucan rich polysaccharides and 3 major metabolites being betulin, betulinic acid, and inotodiol that give Chaga its strong antioxidant properties. A Chaga extract was evaluated for its potential to protect DNA in human lymphocytes against oxidative damage and it was found that cells pretreated with the extract showed over a 40% reduction in DNA fragmentation comparative to a control group.
In a 2007 study conducted by Niigata University of Pharmacy, a hot water extract of multiple medical fungi was measured for each of their antioxidant activity and it showed that Chaga has the strongest activity among all. Chaga has also been proven to have very strong anti-inflammatory effects specific to gut healing. An overgrowth of aggressive bacteria can affect the guts microbiome which has been related to systemic inflammation, thought to be a leading agent for numerous chronic diseases.
A 2017 study conducted by the People’s Republic of China reveals that the polysaccharides of I. obliquus greatly decreased sequence numbers and operational taxonomic units due to the loss of gut microbiota.
This provided space for healthy gut bacteria to colonize and it was concluded that the polysaccharides present in l. Obliquus even promote healthy bacteria growth as well as aid in the regulation of microbial composition.
Lion’s Mane (Hericium erinaceus)
Lion's Mane is a medicinal mushroom thats native to North America, Europe, and Asia and can be identified by its long white, shaggy spines. It appears on hardwood trees and has a tendency to grow just a single clump of dangling spines.
The chemical constituents of H. erinaceus have been investigated for its interesting and significant bioactivities. A variety of terpenoids (diterpenes and sesterpenes) are found in the fruiting body and mycelium of Lion’s Mane. Hericenones and erinacines. Hericenones were typically found in the fruiting bodies while erinacines were derived from the mycelia of the mushroom
One thing that’s interesting about the active constituents in mushroom is that hericenones have only been reported in the fruiting body and erinacines only in the mycelia. It has been proven in a study conducted in 2010 by The Department of Traditional Chinese Medicine that oral administration of erinacines significantly increases levels of NGF in the brain of mice. Specific to the locus coeruleus and hippocampus, but not in the cerebral cortex. NGF stands for Nerve Growth Factors and it is essential for the maintenance, growth, regulation, proliferation, and survival of certain target neurons.
Turkey Tail (Trametes versicolor)
Turkey Tail is found all around the world and is extremely common in North American forests. It got its name because it really takes on the shape of a turkey’s tail. They can grow on just about any dead hardwood logs and stumps in the forests and its cap colors vary dramatically. They tend to be brown, orange, red, and grey.
Medicinally, they are well known for their extraordinary immune enhancing properties. The active immunomodulators present in T. versicolor include polysaccharide krestin (PSK), and polysaccharide-peptide (PSP). PSK is actually an approved drug that’s paid for by national health care in Japan. It’s given orally, along with several chemotherapy protocols. There are numerous in vivo and in vitro studies that show enhanced immune function, antiviral effects, and cholesterol-regulating effects. many turkey tail extracts are specialized, known as PSK or PSP.
Some clinical trials of PSK in cancer treatment began in the 1970s in Japan.
A 2008 study conducted by a group of researchers at Bastyr University stated that based on three decades of clinical research in Asia, PSK as adjuvant therapy is indicated for cancers of the stomach, esophagus, nasopharynx, rectum, colon, and lung and breast. With that said, most of the clinical research focused on the effects of T. versicolor therapy on disease-free and overall survival rates.
They refer to a 1984 study conducted by a research group at Kyushu University.
They published an uncontrolled observational retrospective analysis of breast cancer patients that had recurrent diseases. The patients received chemotherapy with and without PSK immunotherapy. It was very clear that the survival rate after recurrence was significantly extended by PSK immunotherapy.
Another group of researchers conducted a 5-year postoperative randomized controlled trial with 376 women that had stage II ER-negative breast cancer. In this study, they compared chemotherapy with PSK immunotherapy.
The women either received prodrug, 5-fluorouracil or 3,000 mg/d of PSK. The results showed that the 5-year overall and relapse-free survival rated for ER-negative patients were the same whether they received chemotherapy alone or PSK alone.
Cordyceps (Cordyceps sinensis)
Cordyceps has a rich history in traditional medicinal use that dates back thousands of years as well as some extensive clinical research that dates back to the late 1950s.
This mushroom is really interesting in the way that it reproduces because it’s actually another parasitic fungus, kind of like Chaga! Instead of using a tree for a host as Chaga does, Cordyceps uses insects and arachnids. The species with the most promising medicinal benefit is called Cordyceps sinensis and in nature, it sticks with a caterpillar as its host. It takes over the tissues of the caterpillar and starts to grow tall, thin, and dark spores towards the sky. These spores are what harness all of the medicinal potential. While Cordyceps might seem really freaky at first, they have been consumed as a tonic and aphrodisiac in Traditional Chinese Medicine (TCM) for well over two thousand years.
To break it down, there are a few types of supplement forms on the market today that are sold as Cordyceps sinensis. The reason being is that many scientists have had trouble cultivating it so what they ended up with is anamorphs. Anamorphs are mycelium cultures that are unable to produce a fruiting body. These anamorphs are grown in liquid fermentation to create mass amounts of pure mycelium, which is a common process known as liquid culture mycelium. They have been studied extensively and were found to have very similar effects to wild-crafted Cordyceps sinensis. The anamorph is now called Cordyceps Cs-4 or CS4 for short. CS4 is even recognized as a safe natural drug product in China.
There are many bioactive components of Cordyceps that have been extracted and studied. These include nucleosides, polysaccharide, sterol, proteins, amino acids, and polypeptides. These constituents are shown to have anti-inflammatory, anti-oxidant, anti-tumor, and immunomodulatory actions. CS4 has two principal constituents: cordycepin and cordycepic acid. Cordycepin is an adenosine derivative from Cordyceps. It is proven to improve your bodies ATP which may, in turn, enhance the way your body uses oxygen, specifically while exercising.
In a randomized double-blind placebo-controlled clinical trial funded by the Department of Respiratory Disease at Peking Union Medical College Hospital, researchers tested the exercise capability of 30 healthy, mature adults. The participants received either 3 grams of CS-4 or 3 grams of a placebo. It was found that at the end of the 6-week study the participants that received CS4 had a 7% increase of VO2 max. In a similar study with younger adults taking a blend of mushrooms containing C. sinensis that after 3 weeks they had an 11% increase of VO2 max.
VO2 max is a measurement that determines fitness levels. It is defined as oxygen uptake attained during maximum intensity exercise.
And lastly, In regards to its potential to enhance immune system function and overall gut health, a study showed that a C. sinensis hot water extract significantly lowered harmful bacteria populations and increase helpful bacteria in the small intestine of broiler chicks. The chicks were given 600 mg/kg a day for 35 days. The study showed that C. sinensis is helpful in the regulation of intestinal bacteria. In summary, “studies reveal that cordyceps has effects on both innate immunity and adaptive immunity. Furthermore, cordyceps also has a modulatory effect on the gut immune system, which may further influence systemic immune function.”
Unearthing the benefits of an l-theanine + caffeine + ashwagandha stack.
Keeping steady stamina going throughout the day gets a little rough as 2 or 3 pm rolls around. To keep energy levels up, traditionally, a trusted supplement is a cup of coffee containing about 100mg of caffeine. Coffee is incredible as it contains nutrients like alkaloids and antioxidants that can benefit your health while also giving you the energy and stimulation needed to start the day. However, it can also cause unwanted inflammation and persistent overstimulation of the HPA-axis. Basically, the overstimulating effect that caffeine has on the adrenal glands causes a minor activation of the bodies fight or flight response. While minor, over time this quickly leads to burnout causing long term imbalance which then becomes a chronic fatigue issue. This has been recently referred to as adrenal fatigue or HPA-axis dysfunction and is one of the most prominent issues that come from an overconsumption of caffeine.
With what we know about all of the good and bad effects of caffeine, we’re bringing forth a way to combat the negative side effects that come with coffee while actually enhancing all of the positives. Stacking L-theanine with caffeine at a 2:1 ratio has been studied for about a decade now and the results are quite impressive. However, specifically stacking 200mg L-theanine + 100mg Caffeine + 500mg Ashwagandha is the beautiful synergistic combination that we’re bringing to the table. We believe that this pairing makes the perfect stack to maintain afternoon energy levels and while the short term boosts in cognition and energy may be the initial reason for utilizing the stack, the true beauty comes from its long term effects.
What is L-theanine & why do we add it to coffee?
L-theanine is a unique amino acid that’s found almost exclusively occurring in green tea leaves. It has modulatory and neuroprotective effects on the brain by stimulating neurotransmitter function, increasing BDNF production and alpha wave production. Using EEG recordings in humans, a 2008 study published in the Journal of Nutrition reported that activity in the alpha frequency band increases as a reaction to L-theanine administration. This has been of interest in the neuroscience community because the alpha rhythm has long been known to be sensitive to overall attentional states.
The study also reports that participants who took an l-theanine and caffeine ratio of 100mg l-theanine to 50 mg caffeine engaged in an attention-switching test and a memory test for both 60 and 90 minutes. The participants all showed a great improvement in speed and accuracy of performance in both tests as well as a reduction in susceptibility to distracting information during the task that involved memory. The results are evidence that proposes L-theanine and caffeine at a 2:1 ratio are beneficial for improving performance on cognitively demanding tasks.
L-theanine has also been shown to significantly increase activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. At alpha frequencies, the brain is awake but relaxed and is associated with clear-minded focus. Think of alpha brain waves as a bridge between beta and theta frequencies. This is when our minds begin to relax but are still cognitive and we are able to effectively process information, problem solve, and store information. It’s the source of creativity and where most of our greatest ideas are developed. Clinical research found back in 1998 found that supplementing orally with 200mg of L-theanine caused a feeling of relaxation during a study among 8 female college students. It was actually shown that the group of women that had the highest levels of anxiety produced the most alpha brain waves after administration.
How this all effects the frequency of our brain waves.
Interestingly, a fast-acting dose of caffeine actually greatly promotes the production of beta waves which then forces us into a beta state or ‘beta brain’ which is a great state to be in when it’s beneficial to productivity. It’s actually thought that one of the purposes of beta waves is to increase our level of cortical arousal. While having access to produce beta brain waves is crucial for us to function well throughout the day the overproduction can cause stress, frustration anxiety, and other high-intensity emotions.
To learn more about how to take control of excessive beta brain wave frequencies as well as how to manage stressors, read our post specific to this topic here.
Why we add Ashwagandha to the mix.
Ashwagandha comes in for adrenal support. Being a strong anti-inflammatory and adaptogenic herb it can counteract those unwanted effects on the HPA-axis by helping to maintain homeostasis while providing mood and energy support. Speaking long-term, adaptogens build adaptive energy that acts as a reserve for cellular energy. They also help to normalize the function of the neuroendocrine system as well as the HPA-axis (hypothalamus-pituitary-adrenal system) in order to work on the fatiguing facets of stress, anxiety, and long working hours.
Ashwagandha has even been proven effective in decreasing unwanted adrenal cortisol.
In a randomized double-blind, placebo-controlled study, participants with a history of chronic stress had their serum cortisol levels tested and after 60 days of administration with 300mg of Ashwagandha extract. The participant's cortisol levels were tested again after 60 days revealing a severe reduction relative to the placebo group.
To delve deeper into Ashwagandha specifically, check out this blog post.
So what makes this specific caffeine+l-theanine+ashwagandha such a great combination?
It’s all in the synergy of them working together. Since l-theanine is known to be amazing at enhancing efficient cognitive function. Its calming effects takes the edge off of caffeine by balancing out the unwanted results that coffee may have on the brain and canceling out jitters, hyperactivity, overstimulation, etc. Protecting the adrenals is Ashwagandhas’ strong suit which makes it such an effective pairing with coffee since caffeine is known to cause adrenals to overwork and produce excess cortisol which leads to fatigue. This is especially beneficial with long-term use for long-term health benefits and may be specifically helpful for those with a caffeine sensitivity because caffeine sensitivity could very well be an effect of fatigued adrenals.
Most importantly, the synergy of caffeine with l-theanine when taken together have been scientifically proven to enhance the potential benefits of all compounds. Adding ashwagandha to the mix makes sure to cover all of the bases needed to acquire a well-balanced cup of coffee for the mind and body.
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Shenoy, Shweta, et al. “Effects of Eight-Week Supplementation of Ashwagandha on Cardiorespiratory Endurance in Elite Indian Cyclists.” Journal of Ayurveda and Integrative Medicine, Medknow Publications & Media Pvt Ltd, 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3545242/.
Simon P., Gomez-Ramirez, et al. “L-Theanine and Caffeine in Combination Affect Human Cognition as Evidenced by Oscillatory Alpha-Band Activity and Attention Task Performance.” OUP Academic, Oxford University Press, 1 Aug. 2008, academic.oup.com/jn/article/138/8/1572S/4750819