Cordycep sinensis (C. sinensis), called ‘Dong Chong Xia Cao’ in Chinese, is an ancient traditional Chinese medicine made from caterpillar fungus that is one of the most commonly used ingredients to treat people with chronic kidney disease or to maintain post-kidney transplant health . Unfortunately, due to unavailability and heavy metal contamination . Cordyceps militaris has been substituted instead and incorporated into over 400 dietary supplements sold in Thailand.
The main different compound between these two species - C. sinensis and C. militaris is adenosine, which is the main compound of cultivated C. sinensis, but cordycepin (3’-deoxyadenosine) is the main compound of cultivated C. militaris [3, 4]. The natural product of C. sinensis contains a very low content of cordycepin . There is a lack of clinical trials to demonstrate that C. sinensis and C. militaris have similar benefits to health and to determine if C. militaris does not cause adverse reactions.
Animal studies often precede human clinical trials in drug development, and Zhou and Yao’s (2013) 28-day repeated toxicity test in rats found that C. militaris powder orally at 0 (control), 1, 2, and 3 g/kg per day resulted in increments of serum aspartate and alanine aminotransferase (AST and ALT) levels suggestive of weak hepatic toxicity . Nephrotoxicity characterized by tubular epithelium degeneration and necrosis was observed at the high dose. C. militaris treatment significantly decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. They concluded that dietary contamination with C. militaris may have renal toxicity potentials, at least in part by causing oxidative damage to the kidney. Suwannasaroj’s study (2021) in Thailandalso tested sub-chronic (90 days) oral toxicity of C. militaris in rats and found that freshly mixed with distilled water at 20 mg/kg/day resulted in an increase in serum creatinine .
In Vietnam there was one report of 60 cases of toxicity following the ingestion of Cordyceps fungus found in infected cicada nymphs ("cicada flowers") utilized in traditional Chinese medicine. Within 60 minutes of ingestion, symptoms occurred including dizziness, vomiting, salivation, mydriasis, jaw stiffness, urinary retention, seizures, agitated delirium, hallucinations, somnolence and coma. None of the patients suffered liver or kidney injury. There was one fatality. The researchers attributed the toxicity to Cicada infected with Ophiocordyceps heteropoda that contains ibotenic acid.
The anti-inflammatory effect of C. militaris and cordycepin is from cyclooxygenase-2 (COX) inhibition while this effect of C. sinensis is from nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-12 inhibitions [3, 8, 9]. The effect of COX-2 inhibition is well demonstrated, that it causes vasoconstriction and decreases blood flow in kidneys .
Despite the lack of safety studies, scientists in Thailand developed the technology to cultivate C. militaris, including plant-based media technology, and launched a new cordycepin in powder and tea product since 2015 [11, 12]. There are various types of culture media to cultivate Cordyceps spp. and some media contain magnesium sulfate, dipotassium phosphate and peptone, which are able to contaminate in cordyceps products and may damage kidneys . The Thai Food and Drug Administration (FDA) has approved manufacturers to cultivate Cordyceps spp. for a dietary supplement ingredient in 2019 . Subsequently, many products containingC. militaris on the market.
Nevertheless, more than 400 dietary supplements of C.militarisare currently being sold in Thailand in various forms, for example cordyceps powder, tea, coffee, energy drink, and an extract of C.militaris, and cordycepin. Cordyceps products sold in Thailand are available as 50 − 1,000 milligrams (mg)/capsules. A recommended dose of C. sinensisand C. militarisis 1–3 gram(s)/day and 4 grams/day, respectively, and it appears to be safe in the general population [15, 16]. The amount of cordyceps in coffee is 20–600 mg/cup. The usage of products containing cordyceps has been increasing in the last few years advertising on television, radio and social media. Although the Criteria for Food Advertisement B.E.2561 in Thailand does not permit the claim that dietary supplements can treat or alleviate diseases, most cordyceps dietary supplements are advertised, claiming that they do have benefits to health such as controlling diabetes orslowing the progression of kidney disease. The pharmacologic effects of C. militaris have been shown in in vitro and in vivo studies,but there are limited clinical trials to prove its benefits to health.
To the best of our knowledge, the nephrotoxicity related to C. sinensis and C. militaris in clinical studies has never been reported. This study is a preliminary report of patients who developed acute kidney injury (AKI) related to legal products containing C. militaris advertised on television and social media in Thailand.