By fresh weight, most commercially available mushrooms are approximately 90% water, 3% protein, 5% carbohydrates, 1% fat, and 1% minerals and vitamins [4]. The most important bioactive compound with potential use for prevention and treatment of human disease are polysaccharides, which are structural components of the fungal cell wall [3]. It is theorized that polysaccharides are responsible for immunomodulatory effects of medicinal mushrooms by binding to certain cell wall receptors and stimulating specific immune responses [3]. Polysaccharides are also thought to contribute to antitumor, antioxidant, anti-inflammatory, antimicrobial, and antidiabetic effects of medicinal mushrooms [3]. Another important bioactive compound in medicinal mushrooms are terpenes, which modulate the immune system by stimulating the expression of genes implicated in immune responses [3]. They are also thought to have anti-inflammatory, antioxidant, and antitumor properties [3]. Other bioactive constituents of medicinal mushrooms thought to contribute to their medicinal value are proteins, phenolic compounds, antioxidants, copper-containing oxidases, and fatty acids [3].

Agaricusmushroom use may lead to false-positive results on tests that use serum 5-S-cysteinyldopa (5-S-CD) as a marker of tumor growth or recurrence [5]. Elevated serum 5-S-CD levels have been reported in patients takingAgaricusmushroom extracts [5].

In vitro and animal research suggest that polysaccharides in black hoof mushroom could stimulate immune responses, theoretically reducing the effects of immunosuppressant drugs and exacerbating autoimmune diseases, such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), or rheumatoid arthritis (RA) [9]. Due to potential immunostimulant effects, people on immunosuppressant medications or those with autoimmune diseases should either avoid or use black hoof mushroom with caution.

Due to its high oxalate content, excessive ingestion of chaga mushroom can result in acute oxalate nephropathy caused by the deposition of calcium oxalate crystals in the renal tubules [17]. There are two case reports of kidney failure and one case report of acute oxalate nephropathy in patients taking chaga mushroom powder doses of 3–22 grams daily for six months to five years [15]. Renal biopsies showed tubular atrophy, interstitial fibrosis, and the presence of oxalate crystals [15]. In all of these cases, the kidney damage was attributed to the high oxalate content in chaga mushroom [15].

Due to its distinctive appearance, accidental ingestion is rare. However, it is a common cause of mushroom poisoning, especially when it is accidentally consumed by children or people seeking hallucinogenic experiences [19]. Historically, fly agaric mushroom was used by Buddhist monks in the 2nd and 9th centuries to achieve enlightenment [18]. Since boiling or other processing methods eliminates most of the water-soluble toxic compounds in fly agaric mushrooms, some traditional recipes have used it as a homeopathic remedy for neuropathy, fever, and joint pain [20,21].

In vitro research suggests that lion's mane mushroom might inhibit platelet aggregation [22]. Therefore, lion's mane mushroom should be used with caution in combination with drugs, herbs, or supplements with antiplatelet or anticoagulant effects and in people with bleeding disorders due to an increased risk of bleeding.

Animal research suggests that maitake mushroom can lower blood pressure [24]. Therefore, use caution in patients taking antihypertensive drugs or herbs and supplements with hypotensive effects due to the increased risk of additive hypotension.

The cell wall of shiitake mushrooms contains a thermolabile compound called lentinan, which is toxic when consumed raw but safe to eat when heated. As a result, consuming raw shiitake mushroom can cause shiitake dermatitis, a skin eruption resembling whiplash marks which can be accompanied by systemic symptoms [29]. Shiitake dermatitis usually occurs on the trunk and limbs and can look like whiplash marks, small purple spots, skin plaques, burns, blanching, and pustules [29]. In rare cases, the rash looks like measles [29]. Other symptoms associated with shiitake dermatitis include fever, aching, malaise, eosinophilia, diarrhea, prickling in the hands, trouble swallowing, conjunctivitis, and pustules with small ulcers in the mouth [29]. Symptom onset is usually within hours to days and can persist for 3 to 4 weeks before resolving on its own [29]. In some cases, treatment with steroids alone or in combination with antihistamines might reduce the duration of the rash [29].

Most research suggests that oral cordyceps modestly improves kidney function in patients with diabetic nephropathy, or diabetic kidney disease. A meta-analysis conducted in China in patients with diabetic kidney disease shows that taking cordyceps 0.5–2 grams three times daily with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) decreases blood urea nitrogen by 2 mg/dL and decreases serum creatinine levels by 0.1 mg/dL when compared with ACE inhibitor or ARB treatment alone [32]. Another meta-analysis of clinical studies in patients with diabetic kidney disease shows that taking cordyceps as adjunctive therapy to an ACE inhibitor or ARB for 2 to 24 weeks modestly improves markers of kidney function, such as serum creatinine, urea nitrogen, urinary albumin, and total protein, when compared to these medications alone [32].

Turkey tail mushroom constituents PSP and PSK have been officially approved for decades in routine clinical practice in Japan and China as an adjunct to chemotherapy and radiotherapy in doses ranging from 1–3.6 grams daily [3,33]. It has been studied for many different types of cancer, including breast, colorectal, esophageal, gastric, hepatic, leukemia, lung, and nasopharyngeal [33]. Most studies show that taking PSK as an adjunct to standard cancer therapy may improve response rates and survival in some patients with cancer [33]. However, it is unclear whether whole turkey tail mushroom or its constituent PSP is beneficial for patients with cancer [33].

A meta-analysis of 13 clinical trials including over 2,500 patients with esophageal, gastric, colon, rectal, breast, or nasopharyngeal cancer shows that taking PSK in addition to conventional cancer therapy reduces five-year mortality by 9% when compared with conventional therapy alone [33]. When individual cancer types are considered, the benefit of PSK is most evident in patients with breast, gastric, colon, or rectal cancer [33]. Another meta-analysis of 14 clinical trials shows that taking PSK, PSP, or whole turkey tail mushroom in combination with chemotherapy is associated with a 17% lower risk of mortality in some, but not all, types of cancer when compared with chemotherapy alone [33]. However, overall there was no difference in relapse-free survival or total clinical efficacy. The reliability and relevance of these meta-analyses is unclear since there was significant heterogeneity in cancer types, dose and duration of turkey tail mushroom therapy, and type of turkey tail mushroom used. Furthermore, all the included studies were conducted in China or other Asian countries, limiting the generalizability of the results to other populations.