Shiitake

Immune System Enhancement: Lentinan, a β-glucan, is known to stimulate the immune system, potentially aiding in slowing tumor growth and enhancing resistance to infections. Studies indicate it increases immune cell proliferation and activation, such as γδ-T cells and natural killer T (NK-T) cells, and boosts secretory immunoglobulin A (sIgA) in saliva, as seen in a 2015 study involving daily consumption (source).
Antiviral and Antibacterial Effects: Lentinan has shown antiviral effects against poliovirus type 1 and bovine herpes virus type 1, and antibacterial effects by increasing T-helper (Th1) cell immunity and activating macrophage-mediated responses, according to research from Memorial Sloan Kettering Cancer Center.
Antifungal Properties: Shiitake extracts have demonstrated antifungal activity, inhibiting the growth of certain fungal pathogens.
Cancer-Related Effects: Lentinan does not directly kill cancer cells but enhances immune responses that may slow tumor growth. It has been studied for its potential to inhibit leukemic cell proliferation, suppress HIV-1 reverse transcriptase activity, and induce apoptosis in human hepatocellular carcinoma (HepG2) cells via caspase-3 and -8 pathways. A clinical trial showed oral lentinan formulations extending survival in patients with stomach, colorectal, pancreatic, and liver cancers, though a Shiitake extract alone was ineffective for prostate cancer treatment.
Immune Modulation: Shiitake alters immune function by increasing levels of cytokines like IL-1alpha, IL-4, IL-10, and TNF-α, while decreasing MIP-1alpha/CCL3 levels, suggesting a less inflammatory state, as noted in immune studies.
Antihypercholemic Effects: Eritadenine, a compound in Shiitake, regulates lipid metabolism by inhibiting S-adenosyl homocysteine hydrolase and upregulating CYP7A1 mRNA, potentially lowering blood cholesterol. Studies in rats fed Shiitake showed reduced plasma cholesterol levels, attributed to both eritadenine and dietary fiber.
Anti-Obesity Potential: High doses of Shiitake in rat studies prevented obesity by increasing plasma triacylglycerol accumulation in the liver, suggesting a role in fat metabolism regulation.
Other Effects: Shiitake inhibits lung cancer cells via the Latcripin-13 domain, suppresses cytochrome P450 1A enzymes, and increases serum IL-2 levels and TNF-α production, indicating broad pharmacological activity.
Safe Dose Range

Food Consumption: Shiitake mushrooms are generally considered safe when cooked and consumed in typical dietary amounts. Studies and dietary guidelines suggest a range of 50-200 grams per day for healthy adults, based on nutritional intake. For instance, a cup of cooked Shiitake (approximately 145 grams) provides significant nutrients like copper and selenium, and sources like Verywellfit suggest up to 2 cups (290 grams) for balanced diets, though this may be high for daily consumption. FreshCap Mushrooms notes three to eight mushrooms per day, which, at an average weight of 15-20 grams each, translates to 45-160 grams, aligning with this range (source).
Medicinal Use: For medicinal purposes, such as extracts or dried forms, the safe dosage is less defined. A specific extract, AHCC (Active Hexose Correlated Compound), derived from Shiitake, is considered possibly safe at 4.5-6 grams daily for up to 6 months or 3 grams daily for up to 9 years, according to WebMD. Studies on dried Shiitake used doses of 5-10 grams daily, equivalent to about 50-100 grams fresh, showing immune benefits. However, using Shiitake in larger medicinal amounts or raw can be unsafe, potentially causing stomach discomfort, blood abnormalities, and skin reactions like shiitake dermatitis.
Considerations: The literature emphasizes consulting healthcare professionals for medicinal use, especially for those with autoimmune diseases, as Shiitake may increase immune activity, potentially worsening conditions like multiple sclerosis or lupus. Pregnant or breastfeeding individuals should avoid medicinal amounts due to insufficient safety data.

Given the variability, a safe dose range for food is likely 50-200 grams daily of cooked Shiitake, while medicinal doses should be guided by product labels or professional advice, typically 5-10 grams of dried extract daily based on studies.
Safe Dose Range

General Bioavailability: Research indicates that Shiitake’s active compounds, especially polysaccharides, have low oral bioavailability. Lentinan, a key β-glucan, is noted for poor systemic absorption due to its high molecular weight (400-800 kDa) and is often administered intraperitoneally in studies for better efficacy, as mentioned in Drugs.com, due to rapid metabolism and low oral bioavailability. This suggests that oral ingestion may not result in significant blood levels, with effects likely mediated through gut interactions.
Gut Microbiome Interaction: Edible mushroom polysaccharides (EMPs) are resistant to human digestive enzymes and serve as energy sources for gut microbiota, promoting beneficial bacteria growth, as per a PMC review. This implies that their bioactivity is more local, affecting gut immunity and microbiome composition rather than systemic circulation.
Effect of Food (Empty vs. Full Stomach): There is no specific data on whether taking Shiitake on an empty stomach versus with food significantly alters bioavailability. Given that polysaccharides are not readily absorbed and act primarily in the gut, it seems likely that the presence of food would not substantially change absorption, as their effects are mediated through fermentation and immune modulation rather than systemic uptake.
Commercial Claims: Some commercial products, like Hifas da Terra, claim enhanced bioavailability through extraction methods, but these are not backed by peer-reviewed studies for general Shiitake consumption. For instance, a French Mush X post mentions 92% bioavailability for their extracts, but this is a marketing claim without scientific validation.

The safe dose range was inferred from both culinary consumption patterns (50-200 grams daily) and medicinal studies (5-10 grams dried).

Aspect	Details
Pharmacology Actions	Immune enhancement, antiviral, antibacterial, anticancer, cholesterol-lowering, anti-obesity effects.
Safe Dose Range	50-200 grams daily as food; 5-10 grams dried for medicinal use, consult professional.
Oral Bioavailability	Low for active compounds like lentinan; no clear difference with food intake.