Allergic rhinitis (hay fever) in children is a common condition, present more often during certain times of the year, when allergens such as pollen, mould, and dust are in excess. Immunologically it is  characterized by a Th2 polarized immune response and Ig-E antibody production. 

1 in 5 people in the UK experience symptoms of allergic rhinitis which is characterised by the inflammation of the nasal mucous membrane and can also involve the eyes, ears, sinuses, and throat. Commonly linked to conjunctivitis and asthma, allergic rhinitis is a long-standing condition frequently undetected in primary care settings. 

The classic symptoms of the disorder are frequently confused with other respiratory or rhinitis-based symptoms, such as congestion, rhinorrhoea, sneezing, and itching. Thorough physical examinations and allergen testing are recommended for the detection of the condition. Unfortunately, the mainstay treatment of second-generation antihistamines and intranasal corticosteroids are frequently inefficient as a long-term solution. 

Increasing Prevalence of Allergic Rhinitis

Research indicates that up to 40% of the population may already be influenced by rhinitis in some way, characterised by inflammation of the nasal mucosa. Studies also indicate that the prevalence of the disorder is increasing and may be responsible for numerous significant long-term impairments. 

One study into children with allergic rhinitis demonstrated significant learning impairment influenced by the acute symptoms of the condition. Symptoms, including inflammation of the eyes, sinuses, nose, pharynx, larynx, and various areas of the respiratory system, impact concentration. Systematic reviews indicate that frequent exposure to these conditions can be detrimental to sleep, quality of life, and performance in work or school. 

Unfortunately, concentration and quality of life impairments appear to be exacerbated by the use of traditional antihistamine-based treatments. One study found a negative impact on clerical accounting, visual attention, auditory and visual memory, and mathematical skills when taking antihistamine substances. 

Previously, allergic rhinitis was considered a disorder localized specifically to the nasal passages, but further study indicates it may be a component of a systematic airway condition, involving the entire respiratory system. Evidence further shows that inflammation in the upper airway caused by allergic rhinitis may also lead to inflammatory processes in the lower airways, supporting the connection between rhinitis and asthma. 

The Importance of Immunomodulation

Where traditional treatments of allergic rhinitis may have lasting side-effects, natural solutions in the form of medicinal mushrooms could offer a risk-free alternative. Allergic responses stem from hypersensitivity to substances that would otherwise pose no danger to an individual in the environment. 

Common allergic disorders, like allergic rhinitis in children, are influenced fundamentally by the immune system and the body’s production of histamine. Mycomedicine, or the use of medicinal mushrooms, provides timely support for seasonal and year-round rhinitis issues. The Royal Sun Agaricus (Agaricus Blazei Murill) offers proven antihistaminic and immunomodulatory effects as a nutraceutical for allergy treatment. 

The Agaricus blazei mushroom stimulates weakened immune system and brings balance to the Th1 and Th2 responses in the body, which is predominantly Th2 in an allergic rhinitis.  Therefore, its supplementation is useful as an immunomodulator that acts as a natural anti-histaminic remedy. Further biocomponents in the mushroom reduce the release of histamine release in mast cells, lowering allergic response. A clinical study in 2019 showed a reduction of general allergy, asthmatic symptoms and even permitted a reduction in the use of the medication when supplemented with a concentrated mushroom extract based on Agaricus blazei. 

Reishi mushroom (Ganoderma lucidum) further reduces inflammation and reduces the release of histamine release by mast cells. Reishi is also an adaptogen, capable of adapting to various sources of stress by adjusting altered bodily states. Reishi is further suitable for reducing feelings of stress, which can further exacerbate allergic conditions. 

Addressing Inflammation and Microbiota balance

Inflammation is a significant side effect and symptom of allergic rhinitis in children. When exposed to allergens, the body releases substances like histamine which influence swelling. There are various natural approaches to treating inflammation, like eating more foods with anti-inflammatory qualities such as flaxseed and fish. Natural extracts like Reishi mushroom can modulate the immune system response and reduce inflammation simultaneously. 

The high content of anti-inflammatory bioactive compounds in Reishi, triterpenes, gives Ganoderma lucidum an anti-inflammatory action comparable to hydrocortisone without the side effects.  Triterpens, or commonly known as terpens, work alongside other beneficial substances to address the underlying issues of allergic rhinitis in children. 

The consumption of vitamin C alongside mushroom solutions for allergic rhinitis will increase the absorption of some of the bioactive compounds in the substance, such as beta-glucans. Supplemental substances that combine medicinal mushrooms with vitamin C can therefore enhance the natural response of the protocol. Including prebiotics like medicinal mushrooms within the treatment strategy further promotes the growth of healthy bacteria in the microbiota. 

The development of beneficial bacteria can balance the intestinal microbiota which has a long-term impact on children’s health, and their ability to identify viruses and bacteria and differentiate between dangerous and safe entities more effectively. 

Medicinal mushrooms, which are natural prebiotics, together with vitamin C could deliver a long-term solution for allergic rhinitis in children that has none of the dangerous side-effects of traditional treatment routes. These solutions can further be combined with other natural products which offer supportive flavonoids (antioxidants) for helping with inflammation in this condition. 

When dealing with natural products such as medicinal mushrooms, however, it is crucial to ensure the synergised blend of products used in the treatment are concentrated in high quality nutraceuticals, without chemical additives, being as natural as possible and which have been standardized in their active compounds. Preference for organic extracts and quality seals like gluten free or vegan will always indicate that the product has been made with maximum care. 

In the UK, 44% of adults suffer from an allergy. Around half of sufferers have multiple allergies, which accounts for approximately 10 million people [1]. One of the most common is hay fever, clinically known as allergic rhinitis. Characterised by cold-like symptoms, such as a runny nose, itchy eyes, congestion, sneezing and sinus pressure, effective hay fever treatment and prevention is still struggling to cope for clinicians.

Before going further, it is useful to outline the nature of allergies. Essentially, an allergy is an unnatural immune response. The reaction occurs when the presence of foreign peptides in the mucous membranes triggers a Th2 dominant pro-inflammatory state. In the case of hay fever, these foreign peptides could be pollen, dust mites, or particles of skin or saliva shed by pets.

In either context, hay fever is primarily an immunological issue. Therefore, hay fever treatment – and ultimately prevention – should be addressed via immunomodulation. This is what makes medicinal mushroom nutraceuticals such an interesting proposition, which we will explore here.

The Benefits of Agaricus blazei Murill for Hay Fever Sufferers

Agaricus blazei Murill (AbM), or Royal Sun Agaricus, is an edible, medicinal mushroom originating in Brazil. Traditionally, it was used against a range of diseases, including cancer and hepatitis. However, AbM researchers have recently discovered its powerful immunomodulatory properties, which has led to increasing interest [2].

Studies have shown that AbM brings the Th1 and Th2 response into balance, which in regard to hay fever treatment, acts as an anti-histaminic remedy. Achieving this equilibrium due to the specific bio components that inhibit histamine release by mast cells and reduce IgE specific allergy antibodies. The health benefits that arise are both in preventative and therapeutic applications [3]. 

For instance, a clinical study in 2019 showed that, alongside common medical treatment, AbM supplementation yielded a significant reduction of general allergy and asthma symptoms in birch pollen allergic participants [4].

Anti-allergic activities of other Medicinal Mushrooms 

Ganoderma lucidum, or Reishi mushroom, also has been shown to have immune-modulating and immune-potentiating capabilities [5]. Reishi extract contains triterpenes, which generate antioxidant, antihistamine and significant anti-inflammatory activity. In fact, it’s suggested that Ganoderma lucidum has an anti-inflammatory action comparable to hydrocortisone without the negative side effects.

Moreover, in regard to a holistic approach to hay fever treatment, medicinal mushrooms have many benefits. For example, the polysaccharide content of both mushroom species mentioned precipitates a substantial prebiotic effect, which is beneficial for immune function [6].

A Holistic Approach to Hay Fever Treatment   

A holistic, well-being oriented approach to managing hay fever addresses the issue at its root. By supplementing common medical treatments with lifestyle changes, clinicians can seek to prevent allergies as well as treat the symptoms. This could include changes in diet, such as the introduction of therapeutic whole foods like nettles, cleavers, and elderflowers. Equally, onions and apples contain quercetin, which has antioxidant and anti-inflammatory effects. 

However, research is increasingly showing that mushroom nutraceuticals could be one of the most effective lifestyle changes for hay fever treatment. By modulating the immune response and histamine levels, we can address both long-term functional support and current symptoms. Ideally, healthcare professionals should recommend high quality concentrated extracts, preferably organic and standardized in its bioactive compounds. Regarding dosage, it is advisable to adjust it depending on the patient’s evaluation and symptomatology.

References

1. https://www.allergyuk.org/hayfever/allergies-in-the-uk
2. Hetland G, Johnson E, Lyberg T, Bernardshaw S, Tryggestad AM, Grinde B. Effects of the medicinal mushroom Agaricus blazei Murill on immunity, infection and cancer. Scand J Immunol. 2008 Oct;68(4):363-70.
3. Ellertsen LK, Hetland G. An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy. Clin Mol Allergy. 2009;7:6. Published 2009 May 5.
4. Mahmood F, Hetland G, Nentwich I, Mirlashari MR, Ghiasvand R, Nissen-Meyer LSH. Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial. Nutrients. 2019 Oct 2;11(10):2339.
5. Bhardwaj N, Katyal P, Sharma AK. Suppression of inflammatory and allergic responses by pharmacologically potent fungus Ganoderma lucidum. Recent Pat Inflamm Allergy Drug Discov. 2014;8(2):104-17.
6. Wu, H. J., & Wu, E. (2012). The role of gut microbiota in immune homeostasis and autoimmunity. Gut microbes, 3(1), 4–14.

Immune support supplement works as a complement to our immune system. Immunity is a complex system that comprises of several key processes such as activation of macrophages, antigen presentation, and response from lymphocytes. Our body has to create just enough amount of immunity to tackle the pathogens. Too few or too many of them lead to uncontrolled illness and damage to the body systems.

Therefore, immunomodulation works by either boosting or suppressing the immune response towards infections and undesirable conditions. Immunomodulatory agents are often used for treating infections, preventing immunodeficiency, and tumors. Immunomodulators can regulate the immune system to combat infections effectively. In the gut, they stabilize the composition of the gut microbiota by inhibiting harmful microbiota and stimulating health-promoting gut microbiota. 

In an infection, immunomodulators don’t work directly by targeting the pathogens; instead, they modulate the innate and adaptive immune system to combat the condition effectively. This will avoid the development of microbial resistance and can be helpful to immunocompromised patients who cannot take antimicrobial and antiviral drugs.

They are especially critical in oncology cases as they can enhance immunological response to tumor cells. Very recently, immunomodulators are also included in Covid-19 therapy to attenuate the cytokine storm that leads to severe acute respiratory distress syndrome (ARDS).

Mycomedicine in Immune Support Supplement

In the effort of developing natural sources as immunomodulatory agents, medicinal mushrooms are found to be suitable reservoirs of immune-enhancing compounds, experts say. These components have been extensively studied for their ability to modulate the immune system:

1. β-glucans
2. Triterpenoids
3. Lectins

β-glucans work by activating various immune system components such as macrophages, neutrophils, NK cells, and lymphocytes. Combined with oncological treatments, β-glucans can enhance the immune response by binding to pattern recognition receptors that can improve resistance to infections and promote antitumor activity.

Other than having immunomodulatory effects, β-glucans are also known as prebiotics.  β-glucans can induce the growth of Prevotella and Roseburia, the gut microbiota that play critical roles in maintaining health equilibrium. Gut microbiota can boost the immune system, prevent the growth of harmful bacteria, and protect the epithelial integrity. A report shows that unbalanced gut microbiota is often linked with various diseases such as gastrointestinal disorders, obesity, cardiovascular disorders, allergy, and neural diseases. Other studies are highlighting the importance of microbiota modulation in cancer. Even a recent Nature publication states that “gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of colorectal cancer. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed.”

Triterpenoids and lectins have both antiviral and anti-inflammatory activity. These compounds showed a potent inhibitory activity against numerous human patho-genic viruses such as HIV, herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), hepatitis C virus (HCV) and influenza virus. Lectins can also stop the replication of the SARS-CoV virus that causes severe lower respiratory tract infections, as in the Covid-19 disease. Triterpenoids themselves have anti-inflammatory effects by suppressing NF-κB release, blocking DR4 and DR5 pathways, and inhibiting active caspases which all contribute to inflammation process.

Numerous Medicinal Mushroom Species Have Immunomodulatory Effects

Medicinal mushrooms such as Ganoderma lucidum (Reishi), Lentinula edodes (Shiitake), and Grifola frondosa (Maitake), and Inonotus obliquus (Chaga) are well known to exert immunomodulatory effects. Their polysaccharides and protein contents stimulate the activity of the immune components such as B and T lymphocytes, dendritic cells, macrophages, cytokines, and NK cells.

By enabling the immune system, these mushrooms are also able to inhibit tumor growth. Reishi has been proven significant as an adjunctive treatment for lung, leukemia, and prostate tumor. In a 2014 article, Maitake demonstrated its antitumor ability for breast and colon cancer, and Chaga is well-known to be a promising therapeutic agent for hepatocellular carcinoma.

Conclusion

There’s no denying that compounds derived from natural products such as mushrooms are proven to be safe, affordable, and accessible. Medicinal mushrooms are a significant source of nutrients that can be found in an immune support supplement. Immunomodulation is one of the best known health benefits that medicinal mushrooms have to offer. With its abundant bioactive compounds and various health-promoting actions, myco-medicine can help our immune system to combat infections, tumors, and autoimmune diseases. 

 

Mycotherapy is an integrative healthcare practice that uses plants from the fungus family and their derivatives – or, in simple terms, medicinal mushrooms. This term was coined by researchers at biotech Hifas da Terra in 2006, and since, it has become the recognised term for mushroom therapies globally. These fungi and their fractions have various preventative and integrative therapeutic applications, providing support for various pathologies.

Medicinal mushrooms have been prized for their benefits by diverse cultures for centuries. For instance, Ganoderma has been used as a tonic and treatment for various pathologies, including chronic hepatopathy, hypertension, neurasthenia, anxiety, insomnia, bronchitis, gastric ulcer, diabetes, and cancer in China, Japan, Korea, and other Asian countries for over 2,000 years [1]. Meanwhile, Ayurvedic practices similarly revere mushrooms for their holistic nutrition and health benefits.

Today, an increasing amount of scientific evidence is emerging about the efficacy of these traditional medicines which are, in fact, natural nutrients. These studies are demonstrating that mushrooms are indeed potent producers of bioactive substances that can support health and well-being. A single species of medicinal fungus can contain hundreds of bioactive compounds, with hypolipidemic, immunomodulatory and even antitumor activities. 

Certainly, mycotherapy presents exciting prospects for a move towards patient-centred, preventative healthcare. Here, we give an overview of the evidence and discuss why mycotherapy is one of the most innovative tools in integrative therapy today.

Integrative and Innovative Protocols are Changing Healthcare   

Until relatively recently, many healthcare professionals in the Western world subscribed to a reductive view of the body. That is, medicine focussed on disease in its constituent parts, as opposed to the health of the whole. Now, healthcare practitioners are increasingly recognising the benefits of a holistic approach to health, which focus on preventative care and well-being as much as treatment. Taking inspiration from ancient disciplines such as Traditional and Ayurveda, this shift signals a more pluralistic, patient-centred approach to care.

Equally, these disciplines can help to alleviate the side effects triggered by conventional medical treatments. These approaches – captured under the term integrative medicine – neither reject conventional medicine nor adopt alternative methods uncritically. Instead, it acknowledges that medicine should always be open to new research, no matter its biological, cultural, or philosophical basis. This opens healthcare practice to new paradigms of wellness, improving patients’ quality of life.

Broadly speaking, integrative therapy is divided into two main disciplines: mind-body therapies and natural products. Mind-body therapies include manipulative techniques like massage and chiropractors and spiritual practices like yoga or tai chi. Meanwhile, natural products are dietary supplements and nutritional programmes. Mycotherapy falls into this second category to promote overall health and well-being. 

In contrast to traditional phytotherapy or vitamin-mineral supplementation, mycotherapy offers naturally-occurring phytochemicals and vitamins and minerals from a sole source. This is especially beneficial for patients undergoing intensive medical treatments such as chemo- or radiotherapy, who need non-toxic, inert solutions for managing secondarisms.

Emerging Evidence for the Efficacy of Mycotherapy

Now, an increasing amount of research is emerging to support the case for Mycotherapy. This is particularly relevant to patients living with chronic conditions. For example, scientists at the Beijing Normal and Hong Kong Baptist Universities conducted a large scale study on the effect of Ganoderma, Chaga, Coriolus and Maitake mushrooms on patients with chronic bowel complaints. The results were remarkable: there was a marked increase in microbial diversity in the gut and a localised anti-inflammatory response [2].

Furthermore, these benefits extend far beyond the digestive tract. For example, a recent study presented compelling evidence that Mycotherapy has significant benefits for patients living with chronic fatigue. In a study related to athletic performance, Cordyceps and Reishi mushrooms were shown to protect athletes from nonfunctional overreaching (NFO) and overtraining syndrome (OTS). This was measured via salivary cortisol and testosterone levels in cyclists [3].

However, perhaps the most compelling evidence for the holistic health benefits of mycotherapy is its immunomodulatory action provided by medicinal mushrooms and their bioactive immunoregulatory products [4]. Unlike other immunological strategies, immunomodulation consists of providing “soldiers and generals” to our immune system so that it can organize to fight against viruses or cancer cells. In this sense, nutritional supplements based on medicinal mushrooms are different from drugs because they help the body give an orderly response. In addition, the bioactive potential of these compounds has been demonstrated in some remarkable contexts, including oncology.

One such example is a phase 1 clinical trial conducted on women with breast cancer. In the study, researchers applied a fraction of Trametes versicolor, or the Turkey Tail mushroom. After, researchers recorded increased lymphocyte counts, increased natural killer cell functional activity and dose-related increases in CD8(+) T cells and CD19(+) B cells, suggesting this mycotherapy protocol could have significant benefits for immunocompromised breast cancer patients [5].

However, perhaps most relevant to our current moment is research on the immunomodulatory action of mycotherapy in COVID-19. In an ongoing study conducted by Hifas da Terra at a Madrid care home on residents with an average age of 87.2 years diagnosed with COVID-19, fatality rates plummeted from 24.1% to 1.4% after receiving a supplementation based on mushroom nutraceuticals. Equally, more than 88% of the patients who followed the prescribed protocol did not manifest complications associated with COVID-19 and none required admission to the ICU (hospital admission dropped from 27% to 12.3%). These are the first results of a study which is now being extended to other nursing care homes to confirm the efficacy of mycotherapy in a wider population [6].

The Overall Mind and Body Benefits

These immunological properties of medicinal mushrooms mean that Mycotherapy isn’t only useful for supporting treatment – it also has substantial benefits for overall health. For instance, varieties such as Royal Sun Agaricus are rich in proteoglycans, a type of protein important for immune health. Along with beta-glucans and lipids, including linoleic acid and phospholipids, this variety has anti-allergic and immunostimulatory properties [7].

A further example is the Ganoderma or Reishi mushroom. Referred to as ‘the mushroom of immortality’ in Eastern medicinal practices, certain unique compounds of Reishi have impressive anti-inflammatory properties. Moreover, they are thought to be one of the most powerful natural antioxidants in existence, acting on the primary cause of cellular oxidation and ageing [8]. Equally, they are known to have significant antidepressant effects, with various studies demonstrating mood-lifting action [9].

The mental and emotional health benefits of mycotherapy have also been demonstrated with other species. For instance, Hericium erinaceus, a well known edible mushroom, has various biological activities. In a recent study on female patients with depression and sleep disorders, an extract of H. erinaceus was shown to stimulate nerve growth factor (NGF) synthesis, which affects brain function and the nervous system. Results showed that H. erinaceus intake had the possibility to reduce depression and anxiety via its NGF-enhancing action [10].

Selecting Quality Mycotherapy Products

Certainly, there is a wealth of compelling evidence emerging to support the use of mycotherapy in mainstream medicine. However, it is essential that healthcare professionals select quality products. Practitioners should choose ecological, safe and effective supplements developed by experts that are invested in research. As mycotherapy is primarily evidence-based, professionals should trust biotechs that are constantly innovating. 

Biotechs should select strains for their quality, which are further optimised via ecological, organic farming methods. The formulas should contain all of their natural active compounds in their purest form, concentrated and unchanged. Equally, professionals should look for brands with quality assurance standards, where production is uniform, controlled, and regulated by an external organisation such as Good Manufacturing Process (GMP) for pharmaceuticals.

Third party verification is critical across a number of factors; this is especially the case regarding supplements interaction with other medications. Healthcare professionals should preferably look for biotechnology centers that collaborate with external laboratories to verify their safety. Equally, patented formulas and endorsements from regulatory bodies are a hallmark of quality.

Perhaps the most important thing to look for in a mycotherapy product is the manufacturer’s commitment to R&D. As new developments emerge, products should be continually tested and optimised via controlled, clinical trials – this is, after all, the best practice for any medicinal substance. Before selecting a mycotherapy product, explore the biotech’s portfolio of research projects – this will be a good indicator as to their investment in innovation.  

The Future of Mycotherapy

Evidence about the benefits of Mycotherapy is proliferating. Now, there is growing acceptance in the medical community that integrative protocols like mycotherapy have substantial benefits. This is reflected in the growing availability of training in medical schools; according to a survey conducted in 2013, there were 13 American medical schools offering fellowships in integrative medicine.

This is because the evidence is undoubtedly compelling. When it comes to managing the effects of chronic conditions and secondarisms, research has shown that mycotherapy protocols can improve patients’ quality of life. Moreover, patients appreciate this renewed attention to overall well-being; instead of being treated merely as a symptom, integrative therapies position the body as a whole system. In this context, patients feel their unique needs are addressed.

As interest in the field grows, researchers are continuing to innovate. New discoveries are emerging all the time, with far-reaching R&D projects covering everything from anti-ageing ingredients to antiproliferative action on tumours. Looking to the future, mycotherapy could form the basis of innovative bio-pharmaceutical treatments – signalling a natural, integrative, and pluralistic future for modern medicine and complementary therapy. 

References

1. Sanodiya B.S., Thakur G.S., Baghel R.K., Prasad G.B., Bisen P.S. Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol. 2009;10:717–742.
2. Jayachandran, Muthukumaran & Xiao, Jianbo & Xu, Baojun. (2017). A Critical Review on Health Promoting Benefits of Edible Mushrooms through Gut Microbiota. International Journal of Molecular Sciences. 
3. Paola Rossi, Daniela Buonocore, Elisa Altobelli, Federico Brandalise, Valentina Cesaroni, Davide Iozzi, Elena Savino, Fulvio Marzatico, “Improving Training Condition Assessment in Endurance Cyclists: Effects of Ganoderma lucidum and Ophiocordyceps sinensis Dietary Supplementation”, Evidence-Based Complementary and Alternative Medicine, vol. 2014, Article ID 979613, 11 pages, 2014.
4. Zhao S, Gao Q, Rong C, et al. Immunomodulatory Effects of Edible and Medicinal Mushrooms and Their Bioactive Immunoregulatory Products. J Fungi (Basel). 2020;6(4):269. Published 2020 Nov 8.
5. Torkelson CJ, Sweet E, Martzen MR, Sasagawa M, Wenner CA, Gay J, Putiri A, Standish LJ. Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer. ISRN Oncol. 2012;2012:251632.
6. https://hifasdaterra.co.uk/wp-content/uploads/2020/10/EN-NP-trial-nursing-homes-residents.pdf
7. Wang, Hang & Fu, Zhiming & Han, Chunchao. (2013). The Medicinal Values of Culinary-Medicinal Royal Sun Mushroom (Agaricus blazei Murrill). Evidence-based complementary and alternative medicine : eCAM. 2013. 842619. 10.1155/2013/842619.
8. Mohsin M, Negi P, Ahmed Z. Determination of the antioxidant activity and polyphenol contents of wild Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt. Fr.) P. Karst. (higher Basidiomycetes) from central Himalayan hills of India. Int J Med Mushrooms. 2011;13(6):535-44.
9. Matsuzaki H et al., (2013) Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats. BMC Complementary and Alternative Medicine 13, 370.
10. Anderson KO, Getto CJ, Mendoza TR, Palmer SN, Wang XS, Reyes-Gibby CC, Cleeland CS. Fatigue and sleep disturbance in patients with cancer, patients with clinical depression, and community-dwelling adults. J Pain Symptom Manage. 2003 Apr;25(4):307-18.