Three Defenders Mushroom Complex by Doctor's Best

LIKELY EFFECTIVE

• Coronary heart disease (CHD). Consuming products containing at least 3.6 grams of soluble fiber, including beta-glucans, per day may reduce the risk of CHD when consumed as part of a diet low in saturated fat and cholesterol. Details: Clinical research shows that a diet containing foods high in beta-glucans, such as oats and barley, reduces the risk of heart disease (2737,4960,4962,4963,4964,4965,4966,4967,4968). In 1993, the FDA approved a health claim stating that consuming products containing at least 3 grams of beta-glucans per day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD (102336). However, clinical studies show that at least 3.6 grams of soluble fiber daily is needed to reduce the risk of CHD (5786,5787,5788,5794,5795,5796).
• Dyslipidemia. Oral beta-glucans modestly reduces low-density lipoprotein (LDL) cholesterol levels. Details: Although some research disagrees, most clinical research shows that taking barley- or oat-derived beta-glucans 3-10 grams daily for up to 12 weeks or yeast-derived beta-glucans 7.5 grams twice daily for 7-8 weeks can reduce LDL and total cholesterol levels when used for up to 12 weeks (5790,5796,7272,17129,34700,34727,34729,34765,34766,34811)(34812,34876). Meta-analyses of available clinical research on oat-derived beta-glucans show that taking at least 3 grams daily reduces LDL cholesterol by around 4-10 mg/dL and total cholesterol by 4-12 mg/dL but does not affect high-density lipoprotein (HDL) cholesterol or triglyceride levels when compared with control diets (92660,97987,112225). Consuming oat-derived beta-glucans also reduces apolipoprotein B (apoB) levels by 0.54 mg/dL when compared with control diets (97987). The effects of oat-derived beta-glucans on cholesterol levels appear to be greater in patients with diabetes and those with higher LDL cholesterol levels (92660,97987). A meta-analysis of available clinical research on barley-derived beta-glucans shows that consuming an average of 6.5-7 grams of beta-glucans daily as part of the diet reduces LDL cholesterol levels by 4.5 mg/dL, total cholesterol levels by 5.6 mg/dL, and apoB levels by 0.54 mg/dL when compared with control diets (98204). The form of beta-glucans used may alter the effect of beta-glucans on cholesterol levels. Some research shows that barley that is highly enriched (75% by weight) with beta-glucans does not significantly affect cholesterol levels. This lack of effect seems to be the result of processing the barley into a highly enriched beta-glucans product (10166). Other clinical research also shows that the processing of beta-glucans products or the food matrix used to make these products might reduce beta-glucans molecular weight and/or solubility and therefore decrease its ability to lower cholesterol levels (10145,34800,34819).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there is interest in using oral or topical beta-glucans for aging, there is insufficient reliable information about the clinical effects of beta-glucans for this purpose.
• Allergic rhinitis (hay fever). It is unclear if oral beta-glucans are beneficial for reducing symptoms of allergic rhinitis. Details: A small clinical trial in patients allergic to ragweed shows that taking specific yeast-derived beta-glucans (Wellmune WGP) 250 mg daily for 4 weeks decreases the number of allergy symptoms by 28% and the severity of allergy symptoms by 52% when compared with placebo (34859).
• Atopic dermatitis (eczema). It is unclear if topical beta-glucans are beneficial for atopic dermatitis. Details: Preliminary clinical research in children and adults with atopic dermatitis shows that applying a specific cream (Imunoglukan P4H, PLEURAN s.r.o.) containing beta-glucans 0.25% 2-3 times daily for 6 months modestly reduces pruritus, intensity of flares, and overall disease severity when compared with the application of a standard emollient (98201).
• Benign prostatic hyperplasia (BPH). Although there is interest in using oral beta-glucans for BPH, there is insufficient reliable information about the clinical effects of beta-glucans for this purpose.
• Cancer. Although there is interest in using oral beta-glucans for cancer, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Canker sores. It is unclear if oral beta-glucans are beneficial for canker sores. Details: Preliminary clinical research shows that taking beta-glucans 10 mg twice daily for 20 days reduces ulcer severity in patients with recurrent aphthous stomatitis when compared with placebo (34763).
• Chronic fatigue syndrome (CFS). Although there is interest in using oral beta-glucans for CFS, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Critical illness (trauma). It is unclear if oral beta-glucans are beneficial for patients with critical illness. Details: Preliminary clinical research shows that taking oat-derived beta-glucans 3 grams daily as part of enteral feeds does not reduce the length of hospital stay, mortality rate, or infection rate when compared with placebo in patients with trauma. However, the length of time on mechanical ventilation was approximately 47% shorter when compared with placebo (100186).
• Diabetes. Small clinical studies in children and adults with type 1 diabetes suggest that beta-glucans do not improve blood glucose levels. It is unclear if oral beta-glucans are beneficial for patients with type 2 diabetes. Details: Some preliminary clinical research in adults with type 2 diabetes shows that consuming oat-derived beta-glucans 3 grams daily in bread for 3 weeks improves insulin resistance and cholesterol levels when compared with control bread (34765). Other preliminary clinical research in patients with type 2 diabetes shows that consuming bread containing oat-derived beta-glucans in a ratio of 7.6 grams per 100 grams of starch daily for 6 months reduces postprandial glucose levels and glycated hemoglobin (HbA1c) when compared with control bread (97986). Additionally, some clinical research shows that replacing a half serving of white rice with beta-glucans-containing barley attenuates increases in postprandial glucose and insulin levels when compared with a full serving of white rice in patients with type 2 diabetes (103887). However, oat-derived beta-glucans 3-3.5 grams daily in bread or soup for 3-8 weeks does not seem to significantly affect fasting plasma glucose levels or HbA1c when compared with control bread or soup (34765,34788). Also, some evidence shows that consuming soup enriched with beta-glucans does not improve cholesterol levels in patients with type 2 diabetes when compared with control soup (34788). The inconsistency in clinical outcomes may be due to differences in the length of treatment, quantity or ratio of beta-glucans consumed, and/or the preparation of the beta-glucans product. In children with type 1 diabetes, consuming a bedtime snack enriched in beta-glucans appears to prevent hypoglycemia prior to midnight, but does not prevent hypoglycemia at later time points when compared with a control snack (34685). In adolescents with type 1 diabetes, a very small clinical study shows that taking a specific oat product (Betaglucare), providing 6 grams beta-glucans, in three divided doses daily for one week is beneficial for glycemic control and variability when compared with a standard diet without beta-glucans or with 3 grams beta-glucans daily. Maximal, mean, and pre- and post-meal blood glucose levels were modestly lower, and minimal blood glucose levels were modestly higher. Most measures of glycemic variability were statistically different, although there were no differences in the durations of hypoglycemia or hyperglycemia between groups (105261). However, a small crossover study in adults with type 1 diabetes shows that taking a specific product (Stomacol, Brainbridge Commerce AB) containing beta-glucans 1.53 grams 3 times daily prior to meals for 2 weeks does not alter blood glucose levels when compared with placebo (97983).
• Exercise-induced respiratory infections. There is conflicting evidence about the effects of beta-glucans on respiratory infections in athletes following competitive events. Details: Taking a specific product containing oat beta-glucans (OatVantage) 5.6 grams daily for 14 days does not reduce the number of sick days or the number of upper respiratory tract infections in trained male cyclists when compared with placebo (34746). However, other clinical research shows that taking yeast-derived beta-glucans 250-500 mg daily for 4 weeks beginning on the day after a marathon reduces the occurrence of symptomatic upper respiratory infections by 33% to 50% within 2-4 weeks of treatment when compared with placebo. Health scores, fatigue, and mood also improved (34860,92659). Additional clinical research in marathon runners shows that drinking a beverage containing yeast-derived beta-glucans 250 mg daily for 45 days prior to, the day of, and 45 days after a marathon does not reduce the duration or number of upper respiratory infections, but does seem to reduce the number of symptomatic days and overall severity of upper respiratory symptoms, when compared with placebo (103886). Finally, clinical research in top athletes also shows that taking a specific product containing mushroom-derived beta-glucans (Imunoglukan P4H, PLEURAN s.r.o.) 200 mg with vitamin C 200 mg daily for 3 months reduces the number of subjects with at least four symptoms of upper respiratory tract infection by approximately 85% when compared with vitamin C alone (34809).
• Fibromyalgia. Although there is interest in using oral beta-glucans for fibromyalgia, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Hepatitis. Although there is interest in using oral beta-glucans for hepatitis, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Hypertension. It is unclear if oral beta-glucans are beneficial for hypertension; the available evidence is conflicting. Details: Preliminary clinical research shows that consuming an oat cereal containing beta-glucans 5.52 grams daily for 6 weeks reduces diastolic and systolic blood pressure when compared with a low-fiber cereal in hypertensive adults (34691). However, other clinical research shows that consuming oat-based cereals enriched in beta-glucans for 12 weeks does not reduce blood pressure in individuals with hypertension. A reduction in blood pressure occurred in a sub-group of these individuals with a body mass index greater than 31.5 kg/m2 (34684,34722).
• Inflammatory bowel disease (IBD). Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in adults with IBD and symptoms of irritable bowel syndrome shows that taking a combination of beta-glucans, inositol, and digestive enzymes daily for 4 weeks, in conjunction with mesalamine, reduces evacuative urgency when compared with mesalamine alone. Taking this combination product also reduces abdominal pain, bloating, and gas when compared with baseline, but not when compared with taking mesalamine alone (97984).
• Irritable bowel syndrome (IBS). Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking one pill twice daily of a specific combination product (Biointol, BioActivaL) containing beta-glucans, inositol, and digestive enzymes for 4 weeks reduces pain, bloating, and gas, but not other symptoms of IBS, when compared with no treatment (34818). It is not clear if these effects are due to beta-glucans, the other ingredients, or the combination.
• Laser skin resurfacing. It is unclear if topical beta-glucans are beneficial for improving recovery from laser skin resurfacing. Details: In patients that had received fractional laser therapy for atrophic acne scars, preliminary clinical research shows that topical application of skin care products containing beta-glucans, including dressings, solutions, and creams, (Dermdoc, Songyang Biotechnology Co. Ltd) once daily to one side of the face for 14 days modestly increases hydration and reduces redness when compared with the other side of the face treated with the vehicle alone (105263).
• Lower respiratory tract infections. Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that taking a specific combination product (Stimunex gocce) containing beta-glucans, elderberry extract, zinc, and vitamin D3 does not reduce the number or duration of lower respiratory tract infections when compared with no treatment. In the four months after treatment completion, the number of infections was reduced by about 50%; however, the total number of infections in each group was small. The dose was 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212).
• Lyme disease. Although there is interest in using oral beta-glucans for Lyme disease, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Metabolic syndrome. It is unclear if oral beta-glucans are beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome or at high risk for metabolic syndrome shows that eating 200 grams of bread enriched with 6% barley-derived beta-glucans daily for 4 weeks as part of the diet does not alter most metabolic parameters when compared with baseline. However, there was a small reduction in total cholesterol (100185). The validity of this finding is limited by the lack of a comparator group.
• Multiple sclerosis (MS). Although there is interest in using oral beta-glucans for MS, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Neuroblastoma. It is unclear if oral beta-glucans is beneficial in children or young adults with neuroblastoma. Details: Clinical research in children and young adults with relapsed or refractory high-risk neuroblastoma shows that taking yeast-derived beta-glucans for 17 days, starting four days before treatment with intravenous anti-GD2 murine monoclonal antibody for a total of 10 days, results in progression-free and overall survival rates of 28% and 61%, respectively, after 2 years, and 19% and 36%, respectively, after 5 years. Doses of beta-glucans ranged from 10-200 mg/kg daily and each patient completed 1-4 treatment cycles (109203). The validity of these findings is limited by the lack of statistical comparison to a control group. A large clinical study in children and young adults with high-risk neuroblastoma receiving subcutaneous GD2/GD3 vaccine shows that taking beta-glucans 40 mg/kg/day for 14 days as a primer to the vaccine improves the IgG antibody response at 32 weeks when compared with controls who started taking beta-glucans 6 weeks after vaccination. However, taking beta-glucans prior to vaccination does not improve overall or progression-free survival at approximately 20 months (112227). This study may have been inadequately powered to detect a difference in survival between groups.
• Obesity. It is unclear if oral beta-glucans are beneficial for obesity. Details: A meta-analysis of 20 randomized controlled trials shows that taking beta-glucans reduces body weight by about 0.8 kg and body mass index (BMI) by about 0.6 kg/m2 when compared with not taking beta-glucans. However, there was no effect on waist circumference. Also, populations included in this meta-analysis included those with obesity, as well as healthy individuals and patients with diabetes or hypercholesterolemia (100183). Results from individual clinical trials are mixed, with some showing modest reductions in body weight, BMI, and/or waist circumference, and others showing no effect (34790,98202,98203,100183,109208). This research has evaluated barley-, oat-, or yeast-derived beta-glucans at doses between 0.88-9 grams daily for 0.4-12 weeks (34790,98202,98203,100183,109208). Also, a capsule containing yeast-derived beta-glucans 477 mg has been taken daily for 2 weeks, then twice daily for 4 weeks (98203). Beta-glucans have also been taken in combination with other ingredients. For example, barley-derived beta-glucans 2.2 grams has been mixed with rice and consumed twice daily with meals for 12 weeks (98202) and oat-derived beta-glucans (B-Can, Garuda International, Inc.) 2.5 grams has been taken with green coffee polyphenols 300 mg twice daily for 8 weeks (109208). The inconsistency in clinical outcomes may be due to the heterogenous patient populations, as well as the differing sources, doses, and dosage forms of beta-glucans used.
• Otitis media. Although there is interest in using oral beta-glucans for otitis media, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Postoperative pain. It is unclear if oral beta-glucans are beneficial for reducing abdominal pain after surgery for intestinal polyps. Details: Preliminary clinical research in patients who underwent surgical removal of intestinal polyps shows that eating bread containing barley beta-glucans 3 grams daily for 3 months reduces bloating and abdominal pain when compared with eating bread that does not contain beta-glucans (34813).
• Respiratory tract infections. Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that taking a specific combination product (Stimunex gocce) containing beta-glucans, elderberry extract, zinc, and vitamin D3 reduces the duration of respiratory tract infections by about 1.7 days and modestly improves parent-perceived symptom severity and effectiveness when compared with no treatment. However, there was no effect on the number of total, upper, or lower respiratory tract infections, the use of antibiotics or antipyretics, or the number of days missed from school. The product was dosed as 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212).
• Rheumatoid arthritis (RA). Although there is interest in using oral beta-glucans for RA, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Stretch marks (striae gravidarum). It is unclear if topical beta-glucans are beneficial for stretch marks. Details: Preliminary clinical research shows that a specific topical serum and emulsion (Awake; Hangzhou Songyang Biotechnical) containing beta-glucans, applied twice daily for 12 weeks, modestly improves patient-scored, but not physician-scored, stretch mark appearance when compared with a vehicle control. When beta-glucans are used in combination with 1565-nm non-ablative fractional laser once every 4 weeks for 12 weeks, scar atrophy is modestly improved when compared with either treatment alone (109210). However, it is unclear if any changes would be considered clinically significant.
• Upper respiratory tract infection (URTI). It is unclear if oral beta-glucans are beneficial for the prevention of URTIs in adults or children. Details: A meta-analysis of clinical research shows that taking yeast-derived beta-glucans reduces the odds of developing a URTI in generally healthy individuals by approximately 65% when compared with placebo. There was also a small to medium effect on the overall incidence and duration of URTIs. Doses ranged from 35-900 mg daily for 4-26 weeks (105264). However, the results from this analysis were heterogeneous and the number of studies included was small. One study included in the analysis used a specific product containing yeast-derived beta-glucans (Wellmune WGP) 500 mg daily for 12 weeks and found no effect on the number or duration of overall symptomatic infections or the number or duration of specific types of respiratory infections when compared with placebo. However, there was an improvement in quality of life and a reduction in the number of missed work days (34879). Beta-glucans have also been evaluated for the prevention of URTI in children. A small clinical study in children aged 2-6 years with recurrent respiratory tract infections shows that taking a specific combination product (Stimunex gocce) containing beta-glucans, elderberry extract, zinc, and vitamin D3 does not reduce the number or duration of upper respiratory tract infections when compared with no treatment. At four months after treatment completion, the number of infections was reduced by about 44%; however, the total number of infections in both groups was small. The product was dosed as 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212).
• Wound healing. Although there is interest in using topical beta-glucans for healing of wounds, burns, skin ulcers, and dermatitis, there is insufficient reliable information about the clinical effects of beta-glucans for these purposes. More evidence is needed to rate beta-glucans for these uses.

(Read more about BETA-GLUCANS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral lion's mane mushroom is beneficial in patients with Alzheimer disease. Details: Preliminary clinical research in patients over 50 years of age with mild Alzheimer disease shows that taking lion's mane mushroom mycelia (standardized to contain 5 mg/gram of erinacrine A) 1.05 grams daily for 49 weeks improves performance of activities of daily living when compared with placebo. It also improves scores on the Mini-Mental State Examination when compared with baseline (105546). The validity of these findings is reduced by the lack of an intention to treat analysis, and the comparison of some outcomes to baseline instead of placebo.
• Anxiety. Although there is interest in using oral lion's mane mushroom for anxiety, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Athletic performance. Although there is interest in using oral lion's mane mushroom for improving athletic performance, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this purpose.
• Cancer. Although there is interest in using oral lion's mane mushroom for cancer, there is insufficient reliable information about the clinical effects of lions mane mushroom for this purpose.
• Cognitive function. Small clinical trials suggest that lion's mane mushroom does not improve cognitive function. Details: A small clinical trial shows that taking lion's mane mushroom 3.2 grams daily for 12 weeks does not improve most measures of cognitive function when compared with placebo in middle aged to older adults (101770). Additional clinical research in younger adults shows that taking lion's mane mushroom 10 grams daily for 4 weeks does not improve markers of cognition during a period of exercise-induced fatigue when compared with taking placebo. The lion's mane product is 50% dried mushroom and 50% extract (111932). These studies were small and may have been underpowered to detect differences.
• Cognitive impairment. It is unclear if oral lion's mane mushroom is beneficial in patients with mild cognitive impairment. Details: One clinical study in Japanese patients aged 50-80 years old with mild cognitive impairment shows that taking lion's mane mushroom powder 1 gram three times daily for 16 weeks increases cognitive function when compared with placebo. However, cognitive function regresses within 4 weeks of treatment termination (91999).
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral lion's mane mushroom for COVID-19, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this purpose.
• Dementia. Although there is interest in using oral lion's mane mushroom for dementia, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Depression. It is unclear if oral lion's mane mushroom is beneficial in patients with depression. Details: Preliminary clinical research in perimenopausal patients without a formal diagnosis of depression shows that eating 4 cookies daily, each containing 0.5 grams powdered lion's mane mushroom, for 4 weeks is similarly effective to placebo cookies for reducing scores on a depression scale (105547).
• Diabetes. Although there is interest in using oral lion's mane mushroom for diabetes, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Gastritis. It is unclear if oral lion's mane mushroom is beneficial in patients with chronic atrophic gastritis. Details: Preliminary clinical research in patients with chronic atrophic gastritis shows that taking lion's mane mushroom (unknown dose) before meals daily for 3 months improves upper abdominal pain in about 27% more patients, improves dyspepsia in about 39% more patients, and reduces inflammatory infiltration in about 23% more patients when compared with placebo (92630).
• Hyperlipidemia. Although there is interest in using oral lion's mane mushroom for hyperlipidemia, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Memory. Although there is interest in using oral lion's mane mushroom for memory, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this purpose.
• Multiple sclerosis (MS). Although there is interest in using oral lion's mane mushroom for MS, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Obesity. Although there is interest in using oral lion's mane mushroom for obesity, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Parkinson disease. Although there is interest in using oral lion's mane mushroom for Parkinson disease, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Peptic ulcers. Although there is interest in using oral lion's mane mushroom for peptic ulcers, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Wound healing. Although there is interest in using topical lion's mane mushroom for wound healing, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition. More evidence is needed to rate lion's mane mushroom for these uses.

(Read more about LION'S MANE MUSHROOM)

POSSIBLY INEFFECTIVE

• Hyperlipidemia. Preliminary clinical studies show that oral reishi mushroom does not improve lipid levels in patients with hyperlipidemia or type 2 diabetes. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not significantly improve the lipid profile in patients with hyperlipidemia (70776). Also, a meta-analysis shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce total cholesterol or low-density lipoprotein (LDL) cholesterol in patients with type 2 diabetes (91435).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral reishi mushroom for aging, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Altitude sickness. Although there has been interest in using oral reishi mushroom for altitude sickness, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Alzheimer disease. A small clinical study suggests that oral reishi mushroom does not improve Alzheimer disease symptoms. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking reishi mushroom powder 1000 mg three times daily for 6 weeks does not improve memory, language skills, or quality of life when compared with placebo (97942).
• Asthma. Although there has been interest in using oral reishi mushroom for asthma, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Benign prostatic hyperplasia (BPH). Preliminary clinical research suggests that oral reishi mushroom extract can help reduce some lower urinary tract symptoms in patients with BPH. Details: Clinical research in patients with mild to moderate lower urinary tract symptoms (LUTS) associated with BPH, urinary incontinence, overactive bladder, or other conditions, shows that taking reishi mushroom extract 6 mg orally once daily for up to 12 weeks moderately improves total symptom severity measured on the International Prostate Symptom Score (IPSS) scale, when compared with placebo (91436,91437). A higher dose of 60 mg daily is not more effective than the 6 mg dose, and a lower dose of 0.6 mg daily is not more effective than placebo (91437). Reishi mushroom extract does not improve peak urine flow rate, residual urine volume, prostate volume, or quality of life when compared with placebo (91436,91437). The relevance of these results is unclear since not all of the patients with LUTS had BPH.
• Bronchitis. Although there has been interest in using oral reishi mushroom for bronchitis, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Cancer. It is unclear if oral reishi mushroom is beneficial when used in conjunction with chemotherapy. Details: A meta-analysis of 9 clinical trials using various reishi mushroom products in combination with chemotherapy found that complete and partial responses increased by 30% with combination therapy when compared with chemotherapy alone. However, there was no difference in overall survival (102915). The reliability and applicability of these results are unclear since the trials looked at several different types of cancer, used varying doses and durations of therapy, and were all conducted in China or other Asian countries.
• Cancer-related fatigue. It is unclear if oral reishi mushroom is beneficial in patients with breast cancer and fatigue. Details: Results from a small clinical study in breast cancer patients show that taking reishi mushroom powder 1000 mg orally three times daily for 4 weeks can improve cancer-related fatigue when compared with placebo (91438). However, it is not clear if the improvement is clinically meaningful.
• Cardiovascular disease (CVD). It is unclear if oral reishi mushroom is beneficial for reducing CVD risk factors. Details: A meta-analysis of 5 low-quality studies in adults with diabetes shows that taking reishi mushroom 1400-3000 mg daily for 12-16 weeks does not reduce CVD risk factors, including total and low-density lipoprotein (LDL) cholesterol, triglycerides, blood pressure, and body mass index, when compared with placebo (91435).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral reishi mushroom for CFS, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Chronic kidney disease (CKD). Although there has been interest in using oral reishi mushroom for CKD, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Colorectal adenoma. Limited clinical research suggests that oral reishi mushroom extract may be beneficial for reducing colorectal adenoma size. Details: Preliminary clinical research in patients with colorectal adenomas shows that taking reishi mushroom extract 1500 mg orally in two divided doses daily for 12 months reduces the number and size of adenomas when compared with no treatment (70774).
• Coronary heart disease (CHD). It is unclear if oral reishi mushroom is beneficial for CHD. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces symptoms of CHD, such as chest pain, palpitations, and shortness of breath, in a greater percentage of patients when compared with placebo (70800).
• Diabetes. Evidence on the use of oral reishi mushroom in patients with type 2 diabetes is conflicting. Details: A meta-analysis of clinical research in patients with type 2 diabetes shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce glycated hemoglobin (HbA1c) or plasma lipids (91435). However, one preliminary clinical study in patients with type 2 diabetes shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg three times daily for 12 weeks reduces HbA1c, but not fasting blood glucose, when compared with placebo (70801).
• Fibromyalgia. It is unclear if oral reishi mushroom is beneficial for fibromyalgia. Details: A small clinical trial in patients with fibromyalgia shows that taking reishi mushroom (MundoReishi Salud S.L.) powder 3 grams twice daily for 6 weeks does not improve mood, quality of life, anthropometric measures, blood pressure, or glycemic or lipid parameters when compared with placebo (108309,108310). However, the study may have been underpowered to detect any differences between groups.
• Genital herpes. Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent genital herpes shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by 6 days when compared with previous outbreaks (91434).
• Gulf war syndrome. It is unclear if oral reishi mushroom is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in adults with Gulf war syndrome shows that taking reishi mushroom extract (JHS Natural Products, Mushroom Science) 1600 mg in two divided doses daily for 30 days does not improve symptoms when compared with placebo. Also, symptoms modestly worsened after an additional 30 days of treatment at a dose of 3200 mg daily (108311).
• Hepatitis B. One small clinical study suggests that a specific reishi mushroom extract may reduce hepatitis B activity and improve liver function. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces levels of hepatitis B viral DNA and hepatitis B surface antigen, which are markers of hepatitis B activity, and normalizes aminotransferase levels in a greater percentage of patients when compared with placebo (70799).
• Herpes labialis (cold sores). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent herpes labialis shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by almost 4 days when compared with previous outbreaks (91434).
• Herpes zoster (shingles). Although there has been interest in using oral reishi mushroom for herpes zoster, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Human papillomavirus (HPV). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oral HPV shows that taking a combination of reishi and coriolus mushroom powders, 400 mg orally daily for 2 months, clears HPV in 88% of patients when compared with baseline (91433). The validity of this finding is limited by the lack of a comparator group.
• Hypertension. Limited research suggests that oral reishi mushroom may be beneficial in some types of hypertension. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not lower blood pressure in patients with hypertension (70776). However, in other clinical research, taking reishi mushroom extract 330-1440 mg daily for 1-6 months reduces blood pressure in patients with stage II or essential hypertension, but not in those with mild hypertension or diabetes (70786,70802,91435).
• Influenza. Although there has been interest in using reishi mushroom for influenza, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Insomnia. Although there has been interest in using reishi mushroom for insomnia, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Lung cancer. Small clinical studies suggest that oral reishi mushroom does not reduce the size of lung tumors. Details: A meta-analysis of preliminary clinical research shows that taking reishi mushroom does not reduce the size of lung tumors. However, it may stimulate immune function and improve quality of life in lung cancer patients when compared with control (70779).
• Peptic ulcers. Although there has been interest in using oral reishi mushroom for peptic ulcers, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Rheumatoid arthritis (RA). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with active RA who are taking disease-modifying antirheumatic drugs shows that taking reishi mushroom extract 4 grams in combination with San Miao San (containing 2.4 grams each of atractylodes, phellodendron, and Achyranthes bidentata) daily for 24 weeks does not increase the percentage of patients achieving a 20% response based on the American College of Rheumatology (ACR) criteria or modify blood markers of disease and inflammation when compared with placebo (70767).
• Stress. Although there has been interest in using oral reishi mushroom for stress, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose. More evidence is needed to rate reishi mushroom for these uses.

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POSSIBLY INEFFECTIVE

• Dental Plaque. A solution containing an extract of shiitake mushroom is less effective than fluoride mouthwash for reducing dental plaque. Details: Clinical research shows that rinsing the mouth with a solution containing shiitake mushroom extract does not reduce dental plaque when compared with placebo and appears to be less effective than fluoride mouth rinse (Meridol) (94250).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral shiitake mushroom for aging, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Atherosclerosis. Although there has been interest in using oral shiitake mushroom for atherosclerosis, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Breast cancer. Although there has been interest in using oral shiitake mushroom for breast cancer, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Cancer. It is unclear if oral shiitake mushroom is beneficial in patients with cancer. Details: Although some small clinical studies in patients with gastric or colon cancer have found that patients taking the shiitake mushroom extract AHCC 3-6 grams daily have better survival rates and quality of life when compared with historical population data, other observational research has not found a benefit for patients with head, neck, lung, or breast cancer when compared with baseline (30421,30425,30454). The validity of these studies is limited by lack of a comparator group.
• Chemotherapy-induced anemia. It is unclear if oral shiitake mushroom is beneficial in patients with chemotherapy-induced anemia. Details: A small clinical study in adults receiving chemotherapy for pancreatic cancer shows that taking the shiitake mushroom extract AHCC 6 grams daily for 8-12 weeks does not reduce the rate of grade 2 to 3 anemia when compared with placebo (110131).
• Chemotherapy-induced leukopenia. It is unclear if oral shiitake mushroom is beneficial in patients with chemotherapy-induced leukopenia. Details: Preliminary clinical research in patients with breast cancer receiving chemotherapy shows that taking the shiitake mushroom extract AHCC significantly reduces chemotherapy-related neutrophil events and lipid abnormalities when compared with standard care (94829).Observational research in patients with resectable pancreatic ductal adenocarcinoma has found that taking this product orally 3 grams daily throughout 2 cycles of neoadjuvant gemcitabine improves the neutrophil-to-lymphocyte ratio and nutritional scores when compared with standard of care (106783). In contrast, other clinical research in patients with pancreatic or biliary tract cancer receiving gemcitabine chemotherapy shows that taking AHCC 6 grams daily for two months does not seem to affect neutropenia, thrombocytopenia, or hepatic dysfunction when compared with standard of care. However, taking AHCC did reduce C-reactive protein and increase hemoglobin and albumin when compared to standard of care (30424).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral shiitake mushroom is beneficial in patients with CINV. Details: Preliminary clinical research in patients being treated for head and neck cancers shows that taking the shiitake mushroom extract AHCC 3 grams daily, beginning 3 days prior to chemotherapy and continuing until one week after chemotherapy, reduces gastric side effects and the need for antiemetic therapy when compared with baseline (30425). The validity of these findings is limited by the lack of a comparator group.
• Chemotherapy-induced taste changes. It is unclear if oral shiitake mushroom is beneficial for the prevention of taste changes due to chemotherapy. Details: A small clinical study in adults receiving chemotherapy for pancreatic cancer shows that taking the shiitake mushroom extract AHCC 6 grams daily for 8-12 weeks reduces the rate of patient-reported taste disorders by 27% when compared with placebo (110131). Although patients in the AHCC group had modest improvements in some nutritional parameters when compared with the placebo group, it is unclear if any changes would be considered clinically significant.
• Common cold. Although there has been interest in using oral shiitake mushroom for the common cold, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral shiitake mushroom for COVID-19, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Diabetes. Although there has been interest in using oral shiitake mushroom for diabetes, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Genital herpes. Although there has been interest in using oral shiitake mushroom for genital herpes, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Hepatitis C. It is unclear if oral shiitake mushroom is beneficial in patients with hepatitis C. Details: Preliminary clinical research in adults with chronic hepatitis C shows that taking the shiitake mushroom extract AHCC 6 grams daily for 6 months does not significantly reduce alanine aminotransferase (ALT) or hepatitis C virus RNA levels when compared with placebo (30419).
• HIV/AIDS. Although there has been interest in using oral shiitake mushroom for HIV/AIDS, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Human papillomavirus (HPV). It is unclear if oral shiitake mushroom is beneficial in patients with HPV. Details: A small clinical study in adult females with persistent high-risk HPV shows that taking the shiitake mushroom extract AHCC 3 grams daily leads to clearance of HPV RNA and DNA in 64% of patients after 6 months of treatment, compared to 11% of patients taking placebo (110129). The validity of these findings is limited by lack of statistical comparison between groups.
• Hypercholesterolemia. It is unclear whether oral shiitake mushroom is beneficial for lowering blood lipid levels. Details: Clinical research in adults with borderline high levels of cholesterol or triglycerides shows that consuming bars providing shiitake mushroom for 66 days modestly reduces triglyceride levels, but does not affect levels of low-density lipoprotein (LDL) cholesterol or high-density lipoprotein (HDL) cholesterol, when compared with placebo bars. Each bar provided dried shiitake mushroom 3.5 grams daily and the number of bars consumed daily was based on body mass index (108300). The effect of shiitake mushroom in patients with hypercholesterolemia, specifically, is unclear due to the heterogenous patient population.
• Hypertension. Although there has been interest in using oral shiitake mushroom for hypertension, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Impaired glucose tolerance (prediabetes). Oral shiitake mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with prediabetes shows that taking freeze-dried shiitake mushroom 0.96 grams in combination with chokeberry 1.36 grams, Panax ginseng 1.64 grams, and nattokinase 0.8 grams (Chakreis, YD Nutraceuticals Ltd.) twice daily for 12 weeks does not affect glycated hemoglobin, fasting blood glucose, or oral glucose tolerance test results when compared with placebo. However, there were some modest beneficial effects on insulin resistance and fasting insulin and liver transaminase levels (108301).
• Influenza. Although there has been interest in using oral shiitake mushroom for influenza, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Liver cancer. Small, low-quality clinical studies suggest that oral shiitake mushroom extract may improve overall survival in patients with liver cancer. Details: Preliminary clinical research in patients with advanced hepatic cancer shows that taking the shiitake mushroom extract AHCC orally 6 grams daily for a median of 3.5 months along with supportive care increases the median survival time by 2 months when compared with placebo. Taking AHCC also improved quality of life scores when compared with placebo (30359). Population research in patients with hepatocellular carcinoma has also found that taking AHCC 3 grams daily for up to 9 years after surgical resection reduces tumor recurrence and mortality by 48% and 56%, respectively, when compared with control (30353). In another small, open label clinical study of adults with advanced hepatocellular carcinoma, tumor recurrence occurred in 52% of patients who took AHCC 1 gram three times daily for 2 years after surgical resection (110130). The interpretation of these results is limited by the lack of a control group.
• Obesity. Although there has been interest in using oral shiitake mushroom for obesity, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Prostate cancer. It is unclear whether shiitake mushroom has a role in preventing disease progression. Details: Preliminary clinical research shows that taking shiitake mushroom extract does not prevent disease progression, as determined by prostate-specific antigen (PSA) levels, when compared with baseline (10451). More evidence is needed to rate shiitake mushroom for these uses.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Beta-glucans derived from oat bran, baker's yeast, or brewer's yeast (Saccharomyces cerevisiae) have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately, short-term in medicinal amounts. There is some evidence that yeast-derived beta-glucans 15 grams daily can be used safely for up to 8 weeks (7272). Oat-derived beta-glucans 3-10 grams daily can also be used safely for up to 12 weeks (7272,5796,17129,34700,34727,34729,34765,34766,34811,34812)(34876,107935,109206). ...when used topically and appropriately. A specific beta-glucans serum and emulsion (Awake; Hangzhou Songyang Biotechnical) combination has been used with apparent safely for up to 12 weeks in clinical research (109210). A specific beta-glucans cream (Imunoglukan P4H, PLEURAN s.r.o.) has been used with apparent safety 2-3 times daily for up to 6 months (98201).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when an extract of reishi mushroom is used orally and appropriately for up to one year (12,5485,70767,70774,70786,70799,70800,70801,70802). ...when whole powdered reishi mushroom is used orally and appropriately for up to 16 weeks (70776,70799,70800,70801,91433,91435,91436,91437,108309).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using

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LIKELY SAFE ...when consumed in typical food amounts (6).

POSSIBLY SAFE .... ..when the shiitake mushroom extract AHCC is used orally and appropriately. AHCC 4.5-6 grams daily has been used with apparent safety in clinical trials lasting up to 6 months (22926,30419). Population research identified no safety concerns with the use of AHCC 3 grams daily for up to 9 years (30353,94830).

POSSIBLY UNSAFE ...when shiitake mushroom powder is used orally in medicinal amounts. Ingestion of shiitake mushroom powder 4 grams daily for 10 weeks can cause eosinophilia (1149). ...when uncooked shiitake mushroom is ingested. The lentinan component, which is broken down by heat, can cause toxic reactions, including shiitake dermatitis (94354).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid consuming greater than food amounts.

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking beta-glucans with antihypertensive drugs might increase the risk of hypotension.  Details Clinical research shows that taking beta-glucans may reduce systolic and diastolic blood pressure in some hypertensive individuals (34684,34691,34722).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, beta-glucans might interfere with immunosuppressive therapy.  Details Some clinical research shows that beta-glucans have immunostimulant effects (34809,34860,34879,92659,103886,105264).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, lion's mane mushroom may increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.  Details In vitro research suggests that lion's mane mushroom extracts can inhibit platelet aggregation (92619).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, lion's mane mushroom may have additive effects when used with antidiabetes drugs.  Details Animal research suggests that an aqueous extract of lion's mane mushroom can reduce serum glucose and increase serum insulin (91996).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of lion's mane mushroom might interfere with immunosuppressive therapy.  Details In animal and in vitro research, lion's mane mushroom polysaccharides stimulate the immune system (91933,111933).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of reishi mushroom might increase the risk of bleeding.  Details A dose of 1.5 grams daily of reishi mushroom does not seem to decrease platelet aggregation, but a higher dose of 3 grams daily does (5476,13235).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, reishi mushroom might have additive effects with antidiabetes drugs.  Details Animal research suggests that reishi mushroom decreases blood sugar (70769). However, in patients with type 2 diabetes, taking reishi mushroom does not reduce fasting glucose levels, and its effects on glycated hemoglobin are inconsistent (70801,91435).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of reishi mushroom with antihypertensive drugs might increase the risk of hypotension.  Details Reishi mushroom has shown hypotensive activity in animal research (5488,70784). Clinical evidence suggests that reishi mushroom reduces blood pressure in some, but not all, patients with hypertension (70786,70802).

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CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, shiitake mushroom might increase levels of drugs metabolized by CYP2D6.  Details In vitro studies suggest that the shiitake mushroom extract AHCC might induce the CYP2D6 enzyme (30369,30420). This effect has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking shiitake mushroom might decrease the effects of immunosuppressive therapy.  Details In vitro evidence suggests that shiitake mushroom extracts stimulate immune function (30351,30358,30360,30361,30366,30367,30368,30371,30376,30379,30381,30382,30416,30418) (74769,74783,74876,94245).

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General ...Orally and topically, beta-glucans seem to be well-tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis, skin reactions.

Dermatologic ...Topically, a specific beta-glucans cream r.o.) has been reported to cause skin reactions and contact dermatitis in one clinical trial. These reactions occurred in 27% of patients; reactions were mild and self-limiting in 12% of patients (98201).

Hematologic ...In one clinical trial of children and young adults with neuroblastoma, one of 44 patients developed transient elevations of aspartate transaminase and alanine transaminase within five days of starting oral beta-glucans 120 mg/kg daily (109203).

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General ...Orally, lion's mane mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, nausea, skin rash.

Dermatologic ...Orally, lion's mane mushroom may cause skin rash (105546).

Gastrointestinal ...Orally, lion's mane mushroom may cause gastrointestinal discomfort and nausea (91999,105546).

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General ...Orally, reishi mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, dry mouth, itching, nausea, rash, and stomach upset.

Dermatologic ...Orally, reishi mushroom can cause itching, rash, and other skin reactions (12,5479).

Gastrointestinal ...Orally, reishi mushroom can cause dryness of the mouth, throat, or nasal cavity, nausea, stomach upset, and, more rarely, diarrhea (12,70779,91438,108309).

Hematologic ...Orally, reishi mushroom can cause nosebleed and bloody stools (12,91438).

Hepatic ...One case of hepatotoxicity and one case of fatal fulminant hepatitis have been reported in patients who had used reishi mushroom powder for 1-2 months (70766). There is a case report of a 61-year-old male with hypereosinophilia associated with hepatic nodules following the use of reishi mushroom powder for about 2 months. Symptoms resolved after discontinuation of the product. Although these side effects were thought to be associated with the use of reishi mushroom powder, it is unclear if other factors played a role. The patient had been taking tegafur, gimeracil, and oteracil potassium for about 4 months following anterior resection for rectal adenocarcinoma but discontinued these agents and initiated reishi mushroom due to liver injury (108312).

Neurologic/CNS ...Orally, reishi mushroom can cause dizziness (91438). Other rare symptoms include insomnia and headache (70776,70779).

Pulmonary/Respiratory ...Respiratory allergy to reishi spores can occur (12,5479). Sore throat and runny nose have also been reported (70776,91438).

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General ...Orally, shiitake mushroom is generally well tolerated when cooked and consumed as a food.
Most Common Adverse Effects:
Orally: Abdominal discomfort, bloating, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Consumption of raw shiitake mushroom can cause shiitake dermatitis, a skin eruption resembling whiplash marks which can be accompanied by systemic symptoms. Large pieces that have been inadequately chewed can cause intestinal blockage, occasionally requiring surgery.

Dermatologic ...Orally, shiitake mushrooms can cause shiitake dermatitis, a skin eruption that resembles whiplash marks, usually found on the trunk and limbs. This dermatitis is thought to be a toxic response to lentinan or other compounds found normally in uncooked or inadequately cooked shiitake mushroom. The rash can be made worse by scratching. Symptom onset is usually within hours to days and can persist for 3-4 weeks before resolving on its own. There is some evidence that treatment with steroids alone or with antihistamines might reduce the duration of the rash by a small amount in some people (1148,1152,74782,74806,94236,94237,94238,94240,94241,94243) (94244,94246,94247,94248,94249,94252,94253,94254,94255,94256)(94257,94259,94261,94262,108302,111909,111912,111913). The dermatitis may include small purple spots from broken capillaries, skin plaques, burning, blanching, and pustules (94256,108302). Rarely the rash may look like measles rather than whiplash (94256). Histologically, there may be evidence of dermal and epidermal edema, lymphocyte infiltration, and skin thickening (94256,94257). Other symptoms associated with the dermatitis include fever, aching, malaise, eosinophilia, diarrhea, prickling in the hands, trouble swallowing, conjunctivitis, and pustules with small ulcers in the mouth (94240,94246,94247,94249,94256,94257,108302). It is likely that the dermatitis and other symptoms are due to a delayed type hypersensitivity reaction (94244,94255). Cooking shiitake mushroom generally prevents shiitake dermatitis, although some cases have occurred in people who have consumed cooked sources (94242,94244). It appears that to inactivate lentinan, cooking temperatures of at least 130°C are needed (94243).
Less common is a photosensitivity reaction associated with oral ingestion, which involves rash and pruritus after sun exposure (1148,94241).
Orally, the shiitake mushroom extract AHCC has been reported to cause mild itching (30375).

Gastrointestinal ...Orally, shiitake mushrooms can cause abdominal discomfort, including bloating, nausea, pain, vomiting, and diarrhea (1149,30365,30375,30419,94241). Gastrointestinal symptoms, such as diarrhea, problems swallowing, or mouth ulcers have been associated with shiitake dermatitis (94241,94256). Consumption of large pieces of shiitake mushroom with inadequate chewing can cause abdominal obstruction that has resulted in death in one case and surgical intervention in two others. In another case, parenteral nutrition was used exclusively until the shiitake mushroom pieces were passed (1147,94260,103160,108303,108304).
Topically, an oral rinse containing shiitake mushroom extract has been associated with teeth sensitivity, teeth staining, and burning in the mouth (94250).

Hematologic ...Ingestion of shiitake mushroom powder 4 grams daily for 10 weeks caused eosinophilia in 5 of 10 healthy humans (1149). Eosinophilia, and leukocytosis or leukopenia have been reported with shiitake dermatitis (94254,94256,94257).

Immunologic ...Allergic contact dermatitis can occur by contact with shiitake hyphae (filaments) (1153,74785,111913). It appears to be more common in growers or others that handle shiitake mushrooms extensively (94241,94259). Contact or inhalation also results in other symptoms of allergy, such as asthma, rhinitis, conjunctivitis, and pneumonia (94241,94249,94258,94259).

Musculoskeletal ...Orally, the shiitake mushroom extract AHCC has been reported to cause foot cramps and difficulty moving hand joints (30365,30416).

Neurologic/CNS ...In patients experiencing shiitake dermatitis, other symptoms may include prickling in the hands (94256). Malaise has also been reported following oral intake or contact (1151,94240).
Orally, the shiitake mushroom extract AHCC has been reported to cause mild and transient headache (30365).

Ocular/Otic ...Conjunctivitis has been reported rarely in mushroom growers and handlers, or following oral intake in patients with shiitake dermatitis (94241,94256,94259).

Pulmonary/Respiratory ...In mushroom workers, hypersensitivity pneumonitis due to shiitake spore inhalation has occurred. Symptoms include difficulty breathing, chest pain, a dry cough, asthma, and rhinitis (1150,1151,74776,74813,94239,94241,94258,94259).

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