Japanese name – Tochukas
Chinese name – Dong Chong Xia Cao
English name – Caterpillar Fungus
Cordyceps species are unique among the medicinal mushrooms in growing on an insect host rather than a plant host. To date over 700 species of Cordyceps have been identified worldwide, in most cases growing parasitically on their insect hosts. However, it has also been suggested that in some cases a symbiotic relationship exists whereby the insect host derives a selective advantage from the fungal anamorph (the asexual form of the fungus), especially in marginal environments where energy efficiency is at a premium, such as the high Tibetan plateau above 3,000m where the main species used traditionally, Ophiocordyceps sinensis, occurs naturally (although previously part of the Cordyceps genus, molecular phylogenetic analysis has now led to its being placed in a separate genus, the Ophiocordycipitaceae)1,2.
Although traditionally harvested Cordyceps is still available, the vast majority of Cordyceps on the market today is cultivated on non-insect, grain-based substrates leading to improved quality control and affordability. Despite the commercially cultivated Cordyceps being grown on a different substrate from wild collected Cordyceps, HPLC analysis shows identical chemical profiles and the two are seen to be interchangeable clinically3.
As well as polysaccharides and lipids, Cordyceps species contain a large number of nucleoside analogues, prominent among which is cordycepin, 3-deoxyadenosine, which is found in high levels in Cordyceps militaris and which differs from adenosine in the absence of oxygen at the 3 position of its ribose part4-7. Because of its close similarity to adenosine some enzymes cannot distinguish between the two and it is able to participate in certain biochemical reactions, including RNA/DNAsynthesis, where its incorporation leads to the termination of the RNA/DNA molecule, there being no oxygen to bond with the next nucleotide8-11.
This ability to interrupt RNA/DNA synthesis has led to the use of such nucleoside analogues, termed reverse transcriptase inhibitors, in the treatment of viral infections including HIV and hepatitis as well as cancer, under pharmaceutical names including AZT (Retrovir), Videx and Epivir. In normal healthy cells such reverse transcriptase inhibitors are out-competed by the corresponding nucleoside but in rapidly dividing cancer cells and virally infected cells they are able to exert effective inhibition of replication.
Adenosine in the form of adenosine monophosphate (AMP) and adenosine triphosphate (ATP) also plays a central role in energy metabolism and cyclic nucleotides including cAMP play an important role in signal transduction and regulation of hormone production, actions which correlate well with the observed activity of Cordyceps in these areas.
As well as O. sinensis and C. militaris, a large number of trials have been carried out using a fungal strain isolated from wild O. sinensis specimens by China’s Academy of Sciences and selected for ease of cultivation by large-scale liquid fermentation technology. Termed Cs-4, this is currently identified as Paecilomyces hepiali and continues to be one of the main Cordyceps-related species used in China.
One in vitro study, however, showed Cs-4 to have immunosuppressive activity and the immune-suppressant drug Cyclosporin A has been shown to be present in other fungal strains isolated from wild O. sinensis specimens12-14.
ANTI-AGEING – O. sinensis has traditionally been used as a supplement for the elderly and those recovering from long illness. Studies with Cs-4 in healthy elderly subjects showed significant increases in oxygen uptake, aerobic capacity and resistance to fatigue.
Experimental evidence based on polysaccharide extracts indicates that O. sinensis is also able to improve brain function and antioxidative enzyme activity (superoxide dismutase, glutathione peroxidase and catalase), which, together with its beneficial effect on cardiovascular function, makes it an excellent supplement for the elderly15.
ATHLETIC PERFORMANCE – The use of O. sinensis, together with other supplements, by the record breaking Chinese athletes of the early 1990s has attracted considerable interest in its potential to enhance athletic performance.
A 1996 study on long distance runners reported a significant improvement in 71% of participants and O. sinensis and C. militaris as well as the Cordyceps anamorphs Cs-4 and Cs-HK1, have been shown to increase endurance in animal models. Studies on sedentary humans also show a significant increase in energy output and oxygen capacity16-20. However, three studies failed to demonstrate any effect on performance in competitive cyclists or other professional athletes and it has been suggested that this may be because such athletes are already operating at or close to their maximum aerobic capacity21, 22.
SEXUAL FUNCTION – O. sinensis produces clear benefits for male sexual hypofunction when taken over a period of time.Anecdotal evidence and reports from China also indicate possible benefits for female libido.
Based on animal studies O. sinensis and C. militaris have a clear effect on increasing levels of male sex hormones, improving testes morphology, sperm quantity and quality.
In vitro research indicates that Cordyceps affects the signal transduction pathway of steroidogenesis after the formation of cAMP23-27.
FERTILITY – O. sinensis is increasingly being used by leading specialists in the field of infertility and clinical evidence suggests that Cordyceps has a beneficial impact on female fertility and the success of IVF. In part this may be due to its ability to stimulate 17β-estradiol (oestrogen) production, through increased StAR (steroidogenic acute regulatory protein) and aromatase expression28. In common with other mushrooms, Cordyceps’ ability to regulate immune function and in particular NK cell activity may also play a part.
The ability of O. sinensis to increase oestrogen production also has potential for the management of postmenopausal osteoporosis29.
DIABETES – Experimental evidence indicates that O. sinensis is able to:
• Trigger release of insulin
• Increase hepatic glucokinase
• Increase sensitivity of cells to insulin
In one randomized trial 95% of patients treated with 3g/day O. sinensis mycelial biomass saw improvements in their blood sugar profile compared with 54% treated by other methods. In addition it has been reported that consumption of 4.5g/day O. sinensis mycelial biomass by patients with alcohol induced diabetes also produced a reduced desire for alcohol3,30-34.
Recent evidence indicates that Cordycepin and related nucleoside derivatives play an active role in the anti-diabetic action of O. sinensis and that C. militaris, which has high levels of cordycepin, also has significant hypoglycaemic activity35, 36.
HEPATOPROTECTIVE -Multiple studies have shown the ability of both O. sinensis and C. militaris to inhibit hepatic fibrosis and help restore liver function37-39. One clinical study using 3g/day O. sinensis mycelial biomass to treat alcohol-induced liver steatosis in 14 patients showed reductions of 70% in AST levels, 63% in ALT levels and 64% in GGT levels over a 90 day period40.
RENAL HEALTH – O. sinensis has traditionally been considered to support the kidneys and 3.5g/day has been shown to both improve kidney function in patients with chronic renal failure and speed recovery in patients with gentamycin-induced kidney damage3.
RESPIRATORY DISEASE – Traditionally O. sinensis has been used to treat respiratory ailments and is reported to be beneficial for asthma and COPD3.
ANTI-VIRAL – As mentioned above, the nucleoside analogues present in Cordyceps species are able to inhibit viral replication. At the same time the polysaccharides in Cordyceps modulate the immune response to viral infections. This combination of enhanced immune response and interrupted viral replication makes Cordyceps, especially C. militaris, one of the most effective mushrooms for tackling chronic viral infections9,10.
CANCER – Because of its combination of immune-modulating polysaccharides and nucleoside derivatives, many practitioners consider Cordyceps to be one of the most useful mushrooms for helping improve treatment outcomes in cancer, with cordycepin reported to induce apoptosis (cancer cell death) in multiple cancer cell lines, including: oral, colorectal, bladder, leukaemia, melanoma, multiple myeloma, breast and prostate41-52.
CLINICAL SUMMARY
Main Therapeutic Applications – Fertility and sexual function, energy, diabetes, lung function, kidney support, liver disorders.
Key Component – Nucleoside derivatives.
Dose – Cordyceps’ unique properties are principally those of its nucleoside derivatives and as these are largely excreted (research on C. militaris shows that 98% of cordycepin is secreted into the growth medium53) mycelial biomass products offer the natural dosage format for Cordyceps. 2-3g/day mycelial biomass is used in most cases while higher levels have been reported to give good results in a range of cancers2.
Some practitioners prefer to use C. militaris for cancer and viral infections due to its higher cordycepin levels54,55.
Caution – Hormone dependent cancers (prostate and breast) due to increased levels of oestrogen and testosterone.
Although Cs-4 shows benefits for exercise and endurance, possible immune suppression mitigates against its use in immune deficient conditions.
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