Objective: In this study, we evaluated the safety of excessive intake of granular foods containing extract of cultured Lentinula edodes mycelia (L.E.M.) in healthy adult volunteers.
Methods: Eleven subjects (8 males and 3 females, ages 33.4 ± 9.4) consumed the test foods containing 5,400 mg L.E.M. a day, three times the recommended daily intake, for 4 weeks.
Results: No adverse effect by excessive intake of test foods was observed in physical and clinical exam. No severe symptom was observed, except for mild gastrointestinal symptom such as soft stool in a subject who has hypersensitive intestine.
Conclusion: These results suggest that the granular food containing L.E.M. is safe in healthy adults, even if excessive amount up to 5,400 mg a day is consumed.

Objective: Extract from cultured Lentinula edodes mycelia (L.E.M.) is a food ingredient possessing various pharmacologic actions such as immunomodulatory properties, antitumor and hepatoprotective effects. In Japan, it has been used as a health food for 30 years or more.
In the present study to evaluate the safety of L.E.M., a genotoxicity study and acute toxicity study were conducted. In addition, the inhibitory effect of drug-metabolizing enzyme by L.E.M. was tested in vitro, to gain insight on the interaction with medicines.
Methods: The genotoxicity study was performed using a bacterial reverse mutation assay and a in vivo mammalian bone marrow cell chromosomal mutation assay. The acute toxicity study was performed using a single-dose oral toxicity test in rats. Inhibitory activity of cytochrome P-450 3A4 (CYP3A4), one of the most important drug-metabolizing enzymes, by L.E.M. was tested using a baculovirus-expressed system.
Results: In the genotoxicity study, mutagenicity was negative for both bacterial reverse mutation assay and in vivo mammalian bone marrow cell chromosomal mutation assay. In the acute toxicity study, no toxic symptoms were observed by single dose oral administration of L.E.M. at a dose of 10,000 mg/kg BW in rats. This implies LD₅₀>10,000 mg/kg BW. No inhibitory activity of CYP3A4 by L.E.M. was observed at in the in vitro screening system to investigate drug-L.E.M. interaction.
Conclusion: It is believed L.E.M. is a safety ingredient for foods used in complementary and alternative medicine, since it was toxicologically safe and showed no inhibitory activity of CYP3A4 in the studies conducted.