Cordyceps militaris (C. militaris) (L.) Link is an entomopathogenic fungus belonging to the family Cordycipitaceae and the genus Cordyceps. C. militaris is the type species of Cordyceps, which internally parasitizes larva or pupa of lepidopteran insects and forms fruiting bodies on their insect hosts [1-3]. It is one of the most important fungi used in traditional Chinese medicine for the treatment of asthma, and bronchial and lung inflammation [4]. C. militaris possesses extensive bioactive compounds including polysaccharides, cordycepin, adenosine, amino acid, organic selenium, ergosterol, sterols, cordycepic acid, superoxide dismutase (SOD), and multivitamins with significant pharmacological effects [5-7]. C. militaris has been reported to display various biological activities such as anti-cancer [8], immunomodulatory, antioxidant [9], renal-protective [10], antifibrotic [11], antiangiogenetic [12, 13], anti-inflammatory [13], and anti-diabetic [14] activities.
C. militaris has long been recognized as a desirable alternative for Ophiocordyceps sinensis (O. sinensis) based on the similar compositions and bioactive effects of C. militaris and O. sinensis [2, 9, 15-18] as it has been given Chinese Licence number Z20030034/35. The demand for O. sinensis is continuously increasing because of its medicinal uses, while the wild resource is decreasing rapidly due to non-sustainable collection [19]. Hence, O. sinensis is gradually being replaced by large amounts of cultivated C. militaris manufactured by fermentation technology in the marketplace.
For many years, C. militaris mycelium is sold as the dietary supplement in many countries, including USA, Canada, Japan, Korea and China. Taiwan Food and Drug Administration (TFDA) issued notice of the amendment to “Daily consumption limit and Security Marked Warning of the ingredient ‘Cordyceps militaris fruiting body” draft on Jan 12, 2017. In addition to C. militaris fruiting body originally ruled, the manufacturing method and usage amount of C. militaris mycelium are also regulated. Our previous studies demonstrated that no toxic effect was observed in subacute oral toxicity assay [20], 3 different test systems of genotoxicity test [21] and teratogenicity study [22]. Results from these studies suggested that daily treatment with C. militaris mycelium at 3 g/kg BW/day did not induce observable toxicopathologic lesions in male and female rats. However, a 90-day subchronic toxicity study has not yet been conducted for a comprehensive safety profile of this potential mushroom. In the present study, we conducted a 90-day subchronic toxicological assessment of C. militaris mycelium in Sprague-Dawley (SD) rats to confirm the edible safety and evaluate the no-observed-adverse-effect level (NOAEL) of C. militaris mycelium for long term use.
Jhou, B.-Y., et al. (2018). “A 90-Day Subchronic Toxicity Study of Submerged Mycelial Culture of Cordyceps militaris in Rats.” Toxicology Research.