Mushroom extract supplementation: when and how to safely use it

The integration of medicinal mushroom extracts represents one of the most promising frontiers of complementary medicine and contemporary nutraceuticals. This therapeutic approach, rooted in millennia-old traditions, is experiencing an extraordinary revival thanks to growing scientific evidence confirming its efficacy and clarifying its mechanisms of action at the molecular level. Modern mycotherapy does not simply propose basic food supplements but offers a systemic approach to wellness, based on the ability of medicinal mushrooms to modulate gently yet profoundly various physiological functions of the body.

The peculiarity of mushroom extracts lies in their complex biochemical composition, which includes hundreds of active compounds acting in synergy. Unlike the isolated active principles typical of conventional pharmacology, mushroom extracts preserve the integrity of the phytocomplex, ensuring a more physiological and better-tolerated action. This article aims to explore in depth every aspect of integration with mushroom extracts, providing the reader with a comprehensive guide based on the latest scientific findings, but also on the wisdom of traditional medicines that have used these extraordinary organisms for millennia to promote health and well-being.

History and tradition of mycotherapy

The symbiotic relationship between humans and medicinal mushrooms has its roots in the dawn of time, predating the birth of modern scientific medicine by millennia. The first historical evidence of the therapeutic use of mushrooms dates back to the Neolithic period, as attested by archaeological finds demonstrating that 5000 years ago humans had already understood the healing potential of these organisms. However, it is in traditional Chinese medicine that mycotherapy found its most complete and systematic expression. The classic Chinese pharmacology text "Shen Nong Ben Cao Jing", compiled between 200 BC and 200 AD, classifies 365 medicinal substances, including several mushrooms, dividing them into three categories based on their potency and safety of use.

The Reishi mushroom (Ganoderma lucidum) held the place of honor in the hierarchy of medicinal substances, classified in the superior category of "divine herbs" reserved for the emperor and his court. Ancient texts describe it as capable of "strengthening the vital spirit, increasing wisdom, and conferring longevity". Its rarity in nature and cultivation difficulties made it a precious commodity for centuries, accessible only to the upper classes. In parallel, an equally sophisticated approach to the use of mushrooms developed in traditional Japanese medicine, with particular attention to Shiitake (Lentinula edodes), considered not only a delicacy but also a powerful health tonic.

In the West, knowledge of the medicinal properties of mushrooms developed more fragmentarily, often associated with magical and ritual practices. Celtic and Germanic peoples attributed spiritual and curative properties to mushrooms, while references to the use of local species for treating various ailments can be found in the European herbalist tradition. However, it was only with the opening of trade routes with the East and, subsequently, with the development of scientific mycology in the 19th century, that knowledge of the medicinal properties of mushrooms began to spread systematically in the West as well.

Scientific rediscovery in the 20th century: from tradition to evidence

The decisive turning point for modern mycotherapy occurred in the second half of the 20th century, when the international scientific community began to take a serious interest in the medicinal properties of mushrooms. The starting point was the discovery by Japanese researchers of lentinan, a polysaccharide extracted from Shiitake with marked immunomodulatory properties. Clinical studies conducted in the 1960s and 1970s demonstrated that lentinan could enhance the antitumor immune response, paving the way for a new era of research on medicinal mushrooms.

In the 1980s and 1990s, progress in analytical techniques allowed for the identification and characterization of hundreds of bioactive compounds present in medicinal mushrooms. Researchers in Japan, China, Korea, and Europe isolated and studied polysaccharides, triterpenes, lectins, and other active principles, clarifying their mechanisms of action at the molecular level. Concurrently, the development of controlled cultivation techniques made possible the large-scale production of high-quality medicinal mushrooms, overcoming the limitations imposed by wild harvesting and guaranteeing previously unthinkable quality and purity standards.

Today, mycotherapy represents an interdisciplinary field of research involving mycologists, biochemists, pharmacologists, immunologists, and physicians. Scientific publications on the subject number in the thousands and include in vitro studies, animal models, and human clinical trials. While traditional medicine has handed down the empirical knowledge of the properties of mushrooms, modern science is providing experimental proof of their efficacy and the mechanisms that explain it, creating a solid bridge between tradition and innovation that is giving rise to a new, promising frontier of integrated medicine.

Main medicinal mushrooms and their properties

There are many medicinal mushrooms, but the most acclaimed are the following:

Reishi (Ganoderma lucidum): the mushroom of immortality

Ganoderma lucidum, universally known as Reishi (in Japanese) or Lingzhi (in Chinese), undoubtedly represents the most celebrated and studied medicinal mushroom in the history of mycotherapy. Its reputation as the "mushroom of immortality" stems from the unique combination of adaptogenic, immunomodulatory, and neuroprotective properties that make it useful in a wide range of conditions. Botanically, Reishi is a basidiomycete fungus of the Ganodermataceae family, characterized by a shiny red-brown cap and a woody consistency that makes it inedible when fresh but ideal for preparing extracts.

The biochemical composition of Reishi is extraordinarily complex and includes over 400 biologically active compounds identified so far. The main groups of active principles include: polysaccharides (especially beta-glucans with β-(1,3) and β-(1,6) structure), which represent 5-10% of the dry weight and are responsible for the immunomodulatory properties; triterpenes (ganoderic acids), which confer the characteristic bitter taste and possess anti-inflammatory, anti-allergic, and antitumor activity; immunomodulatory proteins (LZ-8); bioactive peptides; and a rich range of minerals, vitamins and antioxidants.

Pharmacologically, Reishi exerts its effects through multiple mechanisms of action. At the immune level, it modulates the activity of macrophages, Natural Killer cells, and T lymphocytes, balancing the Th1/Th2 response and regulating cytokine production. As an adaptogen, it supports adrenal function and helps the body adapt to physical and mental stress. Cardioprotective properties include inhibition of the angiotensin-converting enzyme (ACE), reduction of platelet aggregation, and improvement of the lipid profile. Recent studies have also highlighted interesting neuroprotective properties, with potential application in neurodegenerative diseases.

Cordyceps (Cordyceps sinensis): the natural energizer

Cordyceps sinensis, known as the "caterpillar fungus" for its peculiar ecology (parasitizing insect larvae at high altitudes), is famous for its energizing properties and support for physical performance. In Tibetan and Chinese traditional medicine, it was considered a precious tonic to strengthen the kidney (understood as an energy system according to TCM) and increase vital essence. Today, thanks to bioreactor cultivation techniques, it is possible to produce high-quality Cordyceps without impacting natural ecosystems.

The most important active principles of Cordyceps include cordycepin (3'-deoxyadenosine), a nucleoside analogue with antiviral and antitumor activity; cordycepic acid (mannitol), with diuretic and antioxidant properties; immunomodulatory polysaccharides; and a rich range of nutrients including essential amino acids, B vitamins, and minerals. The most studied mechanism of action relates to energy metabolism: Cordyceps increases ATP production at the mitochondrial level, improves oxygen utilization, and enhances the synthesis of natural corticosteroids, resulting in increased fatigue resistance and improved athletic performance.

In addition to energizing properties, Cordyceps has demonstrated interesting effects on respiratory function (bronchodilation), kidney health (protection from nephrotoxicity), libido and fertility (increased testosterone and improved sperm quality), and the immune system (modulation of innate and adaptive responses). Clinical studies have confirmed its efficacy in improving exercise tolerance, respiratory function in subjects with COPD, and quality of life in patients with chronic fatigue.

Shiitake (Lentinula edodes): the immunomodulating mushroom

Lentinula edodes, commonly known as Shiitake, is the second most cultivated edible mushroom in the world after the button mushroom, but its properties go far beyond nutritional value. Native to East Asia, where it has been consumed for millennia, Shiitake owes its fame as a medicinal mushroom mainly to lentinan, a beta-glucan with extraordinary immunomodulatory properties discovered in the 1960s by Japanese researchers.

In addition to lentinan, Shiitake contains other important active principles including eritadenine, a sulfur compound with cholesterol-lowering properties; lentin, a lectin with antitumor activity; oxalic acid and various aromatic compounds that contribute to the characteristic flavor. Nutritionally, it is rich in complete proteins (contains all essential amino acids), fiber, B vitamins (especially B2, B5, and B6), vitamin D (if exposed to UV light), and minerals such as selenium, copper, and zinc.

The mechanisms of action of Shiitake have been widely studied immunologically. Lentinan activates the complement system, stimulates interferon production, enhances the phagocytic activity of macrophages, and increases the cytotoxicity of Natural Killer cells. These actions translate into greater resistance to viral and bacterial infections and a potential antitumor effect supporting conventional therapies. In parallel, eritadenine inhibits the enzyme homocysteine methyltransferase, reducing homocysteine levels and improving cholesterol metabolism.

Comparative table of main medicinal mushrooms

Nutritional components and active principles

Let's now analyze the main active principles and nutritional components that make medicinal mushrooms so popular

Beta-Glucans: the structural immune modulators

Beta-glucans represent the most important and characteristic class of compounds in medicinal mushrooms, largely responsible for their immunomodulatory properties. Chemically, they are linear or branched polysaccharides consisting of D-glucose units linked by β-(1,3), β-(1,4) or β-(1,6) glycosidic bonds. The specificity of mushroom beta-glucans lies in their branched structure with β-(1,3) and β-(1,6) bonds, which differentiates them from those of cereals (predominantly β-(1,3) and β-(1,4)) and makes them particularly active immunologically.

The mechanism of action of beta-glucans involves interaction with specific receptors present on cells of the innate immune system. The primary receptor is Dectin-1, expressed on macrophages, neutrophils, and dendritic cells, which recognizes β-(1,3) bonds and triggers an intracellular signaling cascade leading to the activation of NF-κB and production of pro-inflammatory cytokines. Other involved receptors include complement receptor 3 (CR3), Toll-like receptors (TLR2 and TLR6), and scavenger receptors. This multimodal interaction explains the potent but physiological immunomodulatory action of mushroom beta-glucans.

In addition to immune properties, beta-glucans have demonstrated beneficial effects on carbohydrate and lipid metabolism. Clinical studies have highlighted their ability to reduce the glycemic index of meals, improve insulin sensitivity, and modulate the lipid profile through inhibition of intestinal cholesterol absorption and stimulation of biliary excretion. These properties make them particularly interesting in the prevention and management of metabolic syndrome and type 2 diabetes.

Triterpenes: the anti-inflammatory and adaptogenic response

Triterpenes are lipophilic compounds of isoprenoid origin that represent the second major class of active principles in medicinal mushrooms, particularly abundant in Reishi (where they constitute 3-5% of the dry weight). Their chemical structure based on the lanostane skeleton confers upon them anti-inflammatory, antioxidant, and selective cytotoxic properties. Reishi triterpenes, particularly ganoderic acids, are responsible for the characteristic bitter taste and possess a marked inhibitory activity on angiotensin-converting enzyme (ACE), explaining the hypotensive properties of this mushroom.

At the molecular level, triterpenes exert their effects through multiple signaling pathways. They modulate the activity of cyclooxygenases (COX-1 and COX-2) and lipoxygenases, reducing the synthesis of pro-inflammatory prostaglandins and leukotrienes. They inhibit nuclear factor kappa-B (NF-κB), a central regulator of the inflammatory response. Some triterpenes, such as ganoderic acid B, have demonstrated selective cytotoxic activity towards tumor cells, inducing apoptosis through caspase activation and disruption of the mitochondrial membrane potential.

In addition to anti-inflammatory and antitumor properties, triterpenes contribute to the adaptogenic action of medicinal mushrooms. Studies on animal models have demonstrated that they can modulate the hypothalamic-pituitary-adrenal (HPA) axis, reducing the corticosterone response to stress and protecting against adrenal exhaustion. This normalizing action on the stress system explains why mushrooms like Reishi are classified as adaptogens - substances that increase the body's non-specific resistance to stressors of various kinds.

Comparative statistics on biochemical composition

Health benefits and mechanisms of action

The ability to modulate the immune system represents perhaps the most studied and documented property of medicinal mushroom extracts. Unlike classical immunostimulants that tend to indiscriminately "push" immune activity, medicinal mushrooms exert a more physiological modulating action, capable of enhancing defenses when necessary (for example in case of infections or neoplasms) and attenuating excessive responses (as in autoimmune diseases or allergies). This balancing is made possible by the complex interaction between the different active principles and the multiple receptors of the immune system.

At the cellular level, mushroom extracts influence practically all populations of the immune system. On macrophages, they increase phagocytic activity, the production of reactive oxygen species (ROS), and the secretion of cytokines like TNF-α, IL-1β, and IL-6. On dendritic cells, they enhance maturation and antigen presentation, improving the synergy between innate and adaptive immunity. On T lymphocytes, they modulate the Th1/Th2/Th17 balance, while on Natural Killer cells they increase cytotoxicity and IFN-γ production. This multi-level action results in a more efficient and balanced immune response.

The clinical applications of immune modulation by medicinal mushrooms are numerous and validated by scientific studies. In oncology, supplementation with extracts of Reishi, Maitake, or Coriolus versicolor during chemo or radiotherapy has been shown to improve patients' quality of life, reduce side effects and, in some cases, enhance the antitumor efficacy of conventional therapies. In infectious diseases, preventive use of Shiitake or Reishi during the flu season can reduce the incidence and severity of infections. In allergies and autoimmune diseases, the ability to rebalance immune responses offers a therapeutic potential that is still underexplored but promising.

Antitumor activity: direct and indirect mechanisms

Interest in the antitumor potential of medicinal mushrooms has ancient origins but received a strong impetus from modern research, which has identified numerous mechanisms of action, both direct and indirect. Direct mechanisms include the induction of apoptosis (programmed cell death) in tumor cells, inhibition of angiogenesis (formation of new blood vessels that feed the tumor), and blocking of metastases through inhibition of matrix metalloproteinases. Indirect mechanisms mainly involve the enhancement of antitumor immune surveillance.

At the molecular level, the active principles of mushrooms act on multiple signaling pathways involved in carcinogenesis. Beta-glucans activate innate immune responses through Dectin-1 and TLR receptors, while triterpenes modulate cell survival pathways such as PI3K/Akt and MAPK. Some specific compounds, like cordycepin from Cordyceps, interfere with protein and DNA synthesis in tumor cells, while others, like betulinic acid from Chaga, induce apoptosis through activation of the mitochondrial pathway. This multimodality of action reduces the risk of developing resistance and increases the potential therapeutic efficacy.

Clinical evidence of the antitumor efficacy of medicinal mushrooms, although still preliminary in some cases, is encouraging. A meta-analysis of 13 randomized controlled trials involving over 1600 cancer patients found that supplementation with Coriolus versicolor extracts (PSK or PSP) during conventional therapies significantly improved 5-year survival in various types of cancer, especially gastric, colorectal, and breast. Studies on Reishi and Maitake have shown benefits in terms of improved quality of life, reduced fatigue, and enhanced immune response. It is important to emphasize that medicinal mushrooms do not replace conventional cancer therapies but can represent a valid complement in an integrated approach under medical supervision.

Metabolic support: from blood sugar to lipids

The potential of medicinal mushrooms to support metabolic health has emerged relatively recently but is attracting increasing scientific interest, especially in light of the global pandemic of metabolic syndrome, type 2 diabetes, and cardiovascular diseases. Several mushrooms, particularly Maitake and Reishi, have demonstrated beneficial effects on glycemic control, lipid profile, and blood pressure, acting through complementary and synergistic mechanisms.

Regarding carbohydrate metabolism, medicinal mushrooms act through multiple strategies. Beta-glucans form viscous gels in the intestinal lumen that slow carbohydrate absorption, reducing the postprandial glycemic peak. Some specific polysaccharides, like grifolin from Maitake, improve insulin sensitivity by increasing the expression of insulin receptors and enhancing insulin signal transduction. Compounds like eritadenine from Shiitake influence homocysteine metabolism, an amino acid associated with insulin resistance when present in excess.

On the lipid front, mechanisms of action include inhibition of intestinal cholesterol absorption (mediated by fibers and specific compounds), stimulation of biliary excretion, modulation of the activity of liver enzymes involved in cholesterol synthesis (HMG-CoA reductase), and regulation of LDL receptor expression. Clinical studies have demonstrated that supplementation with Shiitake extracts can reduce total cholesterol by 7-12% and LDL by 10-15%, while Reishi has shown significant hypotensive effects in hypertensive subjects. These data, combined with the good safety profile, make medicinal mushrooms interesting candidates for integrative approaches to metabolic syndrome.

Types of extracts and preparation methods

Not all extracts are the same, and before starting supplementation, it's good to know the different extraction types in order to choose (always accompanied by your reference specialist) the most suitable one.

Aqueous extracts: maximizing immunomodulatory polysaccharides

The preparation of aqueous extracts represents the most traditional and widespread method for extracting active principles from medicinal mushrooms. This process, which involves the prolonged boiling of the mushroom in water (generally for 8-12 hours), is particularly effective for extracting water-soluble compounds, first and foremost beta-glucans and other immunomodulatory polysaccharides. Temperature and extraction time are critical parameters that influence not only the yield but also the molecular profile of the final extract.

From a technical standpoint, aqueous extraction typically occurs under reflux conditions, which allow for maintaining a constant solvent volume despite evaporation. The temperature is generally maintained between 90°C and 100°C, sufficient to break the cell walls of the mushrooms (mainly composed of chitin) without degrading heat-labile polysaccharides. After extraction, the liquid is filtered to remove solid residues and concentrated by vacuum evaporation, until a dense extract is obtained which can be further dried by spray-drying or lyophilization to produce a fine, stable powder.

The advantages of aqueous extracts include the high concentration of beta-glucans (up to 30-40% in standardized extracts), good bioavailability of water-soluble compounds, and absence of residual solvents. The disadvantages mainly concern the inability to extract lipophilic compounds like triterpenes, which require organic solvents. For this reason, pure aqueous extracts are mainly indicated when the goal is to obtain a specific immunomodulatory effect, while for a more complete action, dual extracts (aqueous + alcoholic) are preferable.

Alcoholic extracts: concentrating lipophilic compounds

Alcoholic extracts, commonly known as tinctures, are prepared by macerating the mushroom in hydroalcoholic solutions with varying strength between 40% and 70% ethyl alcohol. This method is particularly effective for extracting lipophilic compounds like triterpenes, sterols, fatty acids, and phenolic compounds, which are poorly soluble in water but dissolve well in organic solvents. The choice of alcohol strength is crucial: lower concentrations (40-50%) preferentially extract medium-polarity compounds, while higher concentrations (60-70%) are more effective for strongly lipophilic compounds.

The alcoholic extraction process generally involves cold maceration (room temperature) for a duration of 4-8 weeks, with periodic agitation to favor the diffusion of active principles into the solvent. Subsequently, the material is filtered and the solvent is partially evaporated to obtain the desired concentration. The final tinctures typically have a drug/solvent ratio of 1:5 or 1:10 (1 part mushroom to 5 or 10 parts solvent) and can be standardized based on the content of triterpenes or other markers.

The main advantages of alcoholic tinctures include high concentration of triterpenes and other lipophilic compounds, greater stability and shelf life (alcohol acts as a natural preservative), and rapid sublingual absorption that bypasses first-pass liver metabolism. The disadvantages concern the presence of alcohol (contraindicated in some conditions), lower concentration of immunomodulatory polysaccharides, and often very bitter taste due to the high concentration of triterpenes. Tinctures are particularly indicated for obtaining anti-inflammatory, antioxidant, and adaptogenic effects.

Dual extracts: the optimal synergy

Dual extracts represent the most complete and advanced approach to extracting active principles from medicinal mushrooms, combining the advantages of aqueous and alcoholic methods. This method involves the separate preparation of an aqueous extract (for water-soluble polysaccharides) and an alcoholic extract (for lipophilic compounds), followed by their combination in optimal proportions. The result is an extract that preserves the entire spectrum of the mushroom's active principles, ensuring a more complete and synergistic therapeutic action.

The preparation of high-quality dual extracts requires careful optimization of several parameters: the mushroom/solvent ratio for each extraction, the time and temperature of extraction, the degree of concentration of the intermediate extracts, and finally the mixing ratio between aqueous and alcoholic extract. The most qualified manufacturers standardize their dual extracts not only based on the content of specific active principles (e.g., beta-glucans and triterpenes) but also based on the overall biological activity, measured through in vitro tests or animal models.

The advantages of dual extracts are numerous: complete profile of active principles, synergy between water-soluble and fat-soluble components, maximum therapeutic efficacy, and versatility of application. The disadvantages include the higher cost (due to double extraction) and greater production complexity. Dual extracts are considered the premium form and are particularly indicated for specific therapeutic approaches, complex chronic conditions, and when seeking maximum benefit from supplementation. They currently represent the gold standard for high-quality mycotherapy.

When to consider supplementation with mushroom extracts

The use of mushroom extracts for preventive purposes represents the safest and perhaps most logical application of mycotherapy, in line with the Hippocratic principle "prevention is better than cure." From a preventive medicine perspective, supplementation can be considered in various situations of increased risk or particular vulnerability of the organism. The autumn and winter period, characterized by an increase in respiratory infections, represents an ideal time to start a cycle of supplementation with immunomodulatory mushrooms like Reishi, Shiitake, or Maitake, preferably starting 4-6 weeks before the epidemic peak.

Other situations that can benefit from a preventive approach include periods of intense psycho-physical stress (work-related, academic, athletic), during which the organism is more vulnerable to infections and metabolic imbalances. In these cases, adaptogenic mushrooms like Reishi and Cordyceps can help maintain the balance of the HPA axis and improve resilience to stress. Also, advancing age, with the physiological decline of immune function (immunosenescence), represents an important indication for preventive supplementation, preferably with periodic cycles rather than continuous use.

For general prevention, a cyclical approach is typically recommended, with intake periods of 2-3 months followed by 1-month breaks. This scheme helps maintain the reactivity of the immune system and avoid phenomena of habituation or tolerance. Dosages for prevention are generally in the low range of recommendations (500-1000 mg/day of standardized dry extract), possibly increaseable in case of exposure to particular risk factors. It is important to emphasize that preventive supplementation does not replace a healthy lifestyle but represents a valid complement to proper nutrition, regular physical activity, and stress management.

Support in specific conditions: the integrated therapeutic approach

In addition to primary prevention, supplementation with mushroom extracts can be considered in the presence of specific health conditions, always as a complement and not a substitute for conventional medical therapies. In oncology, numerous studies have evaluated the usefulness of mushrooms like Coriolus versicolor, Reishi, and Maitake as adjuvants to standard therapies, with generally positive results in terms of improved quality of life, reduced side effects, and, in some cases, enhanced antitumor efficacy.

In metabolic diseases like type 2 diabetes, metabolic syndrome, and dyslipidemias, mushrooms like Maitake and Reishi offer an interesting complementary approach thanks to their effects on glycemic control, lipid profile, and blood pressure. In neurodegenerative diseases and age-related cognitive decline, Lion's Mane has demonstrated promising effects in supporting neuronal function and synaptic plasticity. In allergies and autoimmune diseases, the modulating capacity of Reishi on the Th1/Th2 balance may offer an approach of regulation rather than immune suppression.

When considering supplementation for specific pathological conditions, it is essential to follow some key guidelines: always consult the treating physician, start with low dosages and increase gradually, carefully monitor the individual response, and prefer high-quality standardized extracts. In many cases, a sequential or rotation approach may be useful, using different mushrooms in succession to cover different aspects of the treated condition. The duration of therapeutic supplementation is generally longer than for prevention (3-6 months or more), with periodic evaluations of efficacy and the need to continue.

How to choose quality products

Choosing a high-quality product is fundamental to obtaining the expected benefits from supplementation with mushroom extracts. The market offers a wide range of products, with significant differences in terms of purity, potency, and bioavailability. To navigate consciously, it is important to check for certifications and quality standards that attest to the product's reliability. Organic certification guarantees that the mushrooms have been cultivated without the use of pesticides, herbicides, or synthetic fertilizers, reducing the risk of contaminants.

In addition to organic certification, it is important to look for products that provide transparent information on purity analysis, verifying the absence of contaminants like heavy metals, mycotoxins, pesticides, and pathogenic microbes. The standardization of extracts is another crucial parameter: quality products indicate the concentration of specific active principles (e.g., beta-glucans, triterpenes) rather than simply the extraction ratio. Good Manufacturing Practices (GMP) attest that the product was manufactured following rigorous quality standards at every stage of production.

Further elements to consider include: the precise botanical species (full scientific name), the part of the mushroom used (fruiting body, mycelium, or both), the extraction method (aqueous, alcoholic, dual), and the presence of excipients or additives. High-quality products tend to contain the minimum necessary excipients, privileging pure forms of extract. Packaging is also important: opaque, well-sealed containers protect the active principles from light and oxygen, preserving their efficacy over time.

Mycelium vs. fruiting body: understanding substantial differences

A fundamental distinction in choosing medicinal mushroom products concerns the use of mycelium or fruiting body. The fruiting body is the visible part of the mushroom, what we commonly identify as the "mushroom," and represents the most active form therapeutically. The mycelium, on the other hand, is the vegetative apparatus of the fungus, consisting of a network of hyphae that extends into the growth substrate. Although the mycelium also contains active principles, their concentration is generally lower compared to the fruiting body.

Mycelium-based products present some significant disadvantages. Since mycelium is typically cultivated on cereal substrates (rice, rye, etc.), the final products can contain a significant percentage of substrate starch, which dilutes the concentration of active principles. Furthermore, the profile of bioactive compounds in mycelium is less complete than that of the fruiting body, which produces a broader range of secondary metabolites in response to environmental stimuli. Finally, scientific research has focused predominantly on fruiting body extracts, so evidence of efficacy for mycelium is more limited.

To ensure maximum efficacy, it is preferable to choose extracts obtained from the fruiting body, possibly integrated with high-quality mycelium when it provides specific compounds. Products should clearly indicate on the label the part of the mushroom used and the relative percentage of fruiting body and mycelium. When in doubt, it is generally better to privilege products that specify "fruiting body extract", as these offer the maximum concentration of active principles and the most complete and studied therapeutic profile.

Resources for further study and verification

For those wishing to deepen their knowledge or verify the reliability of specific products, there are several authoritative resources that can provide scientifically correct and updated information. The Istituto Superiore di Sanità (Italian National Health Institute) offers guidelines on the safety of food supplements and information on substances permitted in Italy. The Società Italiana di Nutraceutica (Italian Society of Nutraceuticals) promotes a scientific approach to nutraceuticals and provides updates on scientific evidence concerning various supplements.

 At the European level, the European Food Safety Authority (EFSA) provides scientific evaluations on the safety of food products and supplements, including those based on mushrooms. These resources can help the consumer make informed choices and distinguish between scientifically founded claims and misleading marketing.

Dosage, safety, and possible side effects

Determining the optimal dosage for medicinal mushroom extracts depends on numerous factors, including the fungal species, the type of extract, the concentration of active principles, the therapeutic goal, and the individual characteristics of the user. In general, for most high-quality standardized extracts, dosages for general prevention range between 500 and 1000 mg per day, while for specific therapeutic objectives higher dosages may be necessary, up to 3000-5000 mg per day.

It is important to emphasize that, despite the generally good safety profile, it is always advisable to start with the minimum effective dosage and increase gradually over 1-2 weeks, carefully observing the individual response. This "start low, go slow" approach allows for minimizing any intolerance reactions or side effects and identifying the optimal dose for each individual. For long-term use, many experts recommend cycles of intake rather than continuous use, for example 3 months of intake followed by 1 month of break, to maintain the organism's reactivity.

The following table provides general guidelines for the dosage of standardized dry extracts of the main medicinal mushroom species. These values are indicative and should be adapted based on individual response and, when necessary, under medical supervision:

Safety Profile: Evidence from Scientific Research

Medicinal mushroom extracts generally have an excellent safety profile when used according to indications and at recommended doses. Numerous toxicological studies, both acute and subchronic, have demonstrated that these products are well tolerated even at dosages significantly higher than therapeutic ones. An acute toxicity study on rats found that Reishi extract showed no significant toxicity even at the dose of 5 g/kg of body weight, corresponding to several hundred grams for a human.

Clinical studies on humans confirm this general safety. In a systematic review analyzing safety data from 31 randomized controlled clinical trials on Reishi, involving over 2300 participants, no serious adverse effects attributable to supplementation emerged. The reported side effects were generally mild and transient, including digestive symptoms (nausea, diarrhea) in a small percentage of subjects, and resolved spontaneously or with a temporary dosage reduction. Similar results have been observed for other medicinal mushrooms like Shiitake, Maitake, and Cordyceps.

Despite the excellent safety profile, it is important to be aware of possible side effects, especially at the beginning of treatment or at high dosages. The most common include mild digestive symptoms (especially with whole mushroom powders rich in fibers), detoxification reactions (headache, fatigue, skin rashes that generally resolve in a few days), dry mouth (particularly with Reishi), and, at very high dosages, blood-thinning effects. These effects are generally manageable by temporarily reducing the dosage and ensuring adequate hydration. 

And, of course, always consult a doctor before, during, and after intake.

Supplementation, drug interactions, and specific conditions

Immunomodulatory mushrooms like Reishi, Maitake, and Shiitake can theoretically interact with drugs that affect the immune system, although specific clinical evidence is still limited. Immunosuppressant drugs (such as cyclosporine, tacrolimus, high-dose corticosteroids), used to prevent rejection in organ transplants or to treat autoimmune diseases, might see their efficacy reduced if associated with immunostimulating mushrooms. Similarly, biological drugs (such as infliximab, adalimumab) used for autoimmune diseases could theoretically interact with the immunomodulatory action of mushrooms.

In case of autoimmune diseases or immunosuppressive therapies, the most prudent approach before starting any supplementation with medicinal mushrooms. If deemed appropriate, a gradual approach can be considered, starting with very low dosages (100-200 mg/day) and increasing slowly under close monitoring of immunological and clinical parameters. In some cases, it might be preferable to use mushrooms with immunomodulatory rather than immunostimulating action (like Reishi) rather than predominantly immunostimulating mushrooms (like Shiitake).

It is important to note that, despite theoretical concerns, some studies suggest that the immune modulation of medicinal mushrooms could be beneficial even in autoimmune conditions, through rebalancing rather than simple stimulation of the immune system. However, given the complexity and potential severity of autoimmune diseases, self-management without medical supervision is strongly discouraged. Careful monitoring by a healthcare professional experienced in mycotherapy is essential in these cases.

Interactions with cardiovascular drugs: essential monitoring

Some medicinal mushrooms, particularly Reishi, have demonstrated effects on the cardiovascular system that could interact with specific drugs. The most documented effect is the anticoagulant/antiplatelet one, observed in in vitro studies and animal models. Reishi, in particular, has been shown to inhibit platelet aggregation and prolong clotting time, effects attributed mainly to its triterpenes. Theoretically, this could potentiate the effect of anticoagulant drugs like warfarin or antiplatelets like aspirin and clopidogrel, increasing the risk of bleeding.

In case of anticoagulant therapy, careful monitoring of coagulation parameters (INR for warfarin) is essential when starting supplementation with medicinal mushrooms. Any significant change in INR should be promptly reported to the doctor, who may eventually adjust the drug dosage. It is also important to inform the doctor before surgical interventions or invasive procedures, as it might be advisable to temporarily suspend supplementation. Signs of abnormal bleeding (easy bruising, gum bleeding, nosebleeds) require immediate medical evaluation.

In addition to anticoagulant effects, some mushrooms (especially Reishi and Maitake) have demonstrated hypotensive properties in clinical studies. These effects could potentiate the action of antihypertensive drugs, causing excessive hypotension. It is therefore recommended to monitor blood pressure regularly when starting supplementation, especially if already taking medication for hypertension. Similarly, the hypoglycemic effects of mushrooms like Maitake could potentiate the action of diabetes drugs, requiring careful blood glucose monitoring and possible therapeutic adjustments.

Supplementation: future research and perspectives

One of the most promising frontiers of research in mycotherapy is the development of personalized approaches based on the genetic, immunological, and metabolic characteristics of each individual. Interindividual variability in response to medicinal mushrooms is a well-known phenomenon in clinical practice, but only recently has research begun to identify the factors that determine it. Pharmacogenomic studies are trying to correlate specific genetic polymorphisms (e.g., in immune receptors or cytochrome P450 enzymes) with the individual response to different medicinal mushrooms.

In parallel, research is exploring the use of specific biomarkers to monitor the response to supplementation with mushroom extracts. These include not only standard blood chemistry parameters but also more sophisticated markers like the cytokine profile, Natural Killer cell activity, overall antioxidant status, and even the gut microbiome profile, which can significantly influence the metabolism and absorption of active principles. The integration of these multivariate data through artificial intelligence and machine learning approaches could lead to the development of predictive algorithms capable of suggesting the most appropriate mushroom, the optimal dosage, and the treatment duration for each individual.

Personalized mycotherapy represents not only an opportunity to maximize treatment efficacy but also to minimize the risk of side effects and interactions. In the future, we might witness the creation of true individual "mycotherapy profiles," based on genetic, immunological, and metabolic tests, which will guide the physician or nutritionist in choosing the most appropriate protocol. This precision approach could revolutionize the use of medicinal mushrooms, transforming them from generic remedies into highly specific and personalized therapeutic tools.

Synergies and combinations: enhancing efficacy through integration

Another particularly active area of research concerns the study of synergies between different medicinal mushrooms and between mushrooms and other nutraceutical or pharmacological compounds. Traditional medicine has always privileged the use of combinations of plants and mushrooms, based on the empirical observation that the synergistic action of multiple components can be superior to the sum of individual actions. Modern science is now seeking to validate and explain these synergies through mechanistic and controlled clinical studies.

At the mechanistic level, synergies can manifest through different mechanisms: enhancement of absorption or bioavailability of active principles, action on complementary signaling pathways, modulation of negative feedbacks, or protection from metabolic degradation. For example, the combination of Reishi (immunomodulatory and anti-inflammatory) with Turmeric (potent anti-inflammatory) might offer superior benefits in managing chronic inflammatory conditions compared to the use of individual components. Similarly, the combination of Cordyceps (energizing) with Rhodiola (adaptogen) might enhance fatigue resistance by acting on complementary mechanisms.

Future research will need not only to identify the most promising combinations but also to optimize the ratios between the different components, the timing of administration, and the intake sequences. Network pharmacology studies are already mapping the complex interactions between the multiple compounds present in mushroom extracts and their molecular targets in the organism, offering a rational basis for the development of synergistic combinations.

These approaches could lead to the creation of integrated therapeutic protocols that strategically combine different medicinal mushrooms with other nutraceuticals, maximizing efficacy through a multi-level action on physiological systems, thus arriving at a synergistic integration.