Cordyceps

Scientific Name(s): Cordyceps sinensis (Berk.) Sacc. Family: Clavicipitaceae

Common Name(s): Cordyceps , aweto , caterpillar fungus , Cs-4 , Dong Chong Xia Cao , keera jhar , keeda ghas , semitake , tochukaso , XinGanBao , yarshagumba , yartsa gunbu , yatsa gunbu , Zhiling

Uses
Well-controlled clinical trials are lacking.

A Joint Effort: A Provider’s Guide To Orthopedic Pain Options
SLIDESHOW
A Joint Effort: A Provider’s Guide To Orthopedic Pain Options
Dosing
Dosing supported by product quality data is unavailable, and many herbal supplements on the market contain varying undefined levels of this product. Cordyceps 3 to 6 g/day has been used in patients with chronic renal failure for periods ranging from days to years.

Contraindications
Contraindications have not been identified.

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions
None well documented.

Adverse Reactions
Mild GI discomfort, including diarrhea, dry mouth, and nausea, has been reported.

Toxicology
Cordyceps is generally considered safe.

Botany
Cordyceps sinensis belongs to a genus of more than 400 species of Ascomycete (sac fungi) found worldwide. It is a black, blade-shaped fungus found primarily in the high altitudes of the Tibetan plateau in China that parasitizes moth caterpillars. In the fall, the fungal mycelia infect the caterpillar, which then kills it by early summer of the following year, releasing spores from the fruiting body (the stroma). The wild form of C. sinensis is rare and expensive; consequently, a strain isolated from the wild form (Cs-4, or Paecilomyces hepiali Chen) is cultivated industrially and more commonly used. Issues of substitution with other species and contamination have been described. 1 , 2 , 3 , 4

History
Tibetan history records the first uses of yartsa gunbu in the 15th century. Cordyceps is considered to be derived from the Latin cord (club), ceps (head), and sinesis (from China). The fruiting body and attached mycelium of cordyceps have been used in Chinese culture and in traditional Chinese medicine for centuries. Cordyceps is valued for its activity in restoring energy, promoting longevity, and improving quality of life. 2 , 4 , 5

Chemistry
The nucleosides adenine, adenosine, uracil, uridine, guanidine, guanosine, hypoxanthine, inosine, thymine, thymidine, and deoxyuridine are the major component of cordyceps and can be used as a species marker. Fresh, natural cordyceps contain a lower content of nucleosides than dry, processed, or cultured cordyceps. 3

Other classes of constituents found in wild C. sinensis include the following: proteins, peptides, all essential amino acids, and polyamines; saccharides and sugar derivatives; sterols; fatty acids and other organic acids; vitamins (including B 1 , B 2 , B 12 , E, and K); and inorganic elements. 2 , 4 , 6 Cordycepin and other adenosine derivatives, ergosterol, mannitol, cordyheptapeptide A, and several other unique compounds have been identified using thin layer and gas chromatography, high-performance liquid chromatography, and capillary electrophoresis. Water, ethanol, methanol, and ethyl acetate extracts have been described for the whole fungus and mycelium, as well as for other parts of the fungus. 3 , 7 , 8

Uses and Pharmacology
In vitro evaluation and animal studies of cordyceps and its chemical constituents suggest potential therapeutic applications; however, despite a significant number of clinical studies, the overwhelming majority had poor methodologies. Very few large, randomized, controlled clinical trials have been conducted (several of which evaluated cordyceps in combination with other agents), making definitive statements about the efficacy of cordyceps premature. 4 , 7 , 9

Aging (senescence)
Traditionally, cordyceps has been used in the elderly population to improve weakness, impotence, and fatigue associated with aging. 4 , 10 Clinical studies have been conducted among elderly subjects; however, the methodology of such studies is often poorly documented. Improvements in self-reported symptoms have been described, as have increases in red blood cell superoxide dismutase activity and decreases in malondialdehyde levels. 2 , 8 Other antioxidant effects, hydroxyl radical scavenging activity, and decreases in lipid peroxidation are thought to be responsible for the antiaging effects, 8 , 11 , 12 as well as effects on the adrenergic and dopamine systems. 13 Increases in learning and memory have been shown in experiments in aged mice. 10

Cancer
Numerous in vitro and animal experiments have been conducted on aqueous and ethanol extracts of cordyceps, as well as with cordycepin and oxypiperazines extracted from the mycelium. The extracts enhanced cytokine activity and induced cell cycle arrest and apoptosis, thereby reducing tumor cell proliferation and enhancing survival times. 4 , 14 , 15 , 16 , 17 , 18 , 19 , 20

Limited clinical studies report subjective improvement of symptoms, increased tolerance of radiation and chemotherapy (possibly caused by enhanced immune function), and reduction in tumor size with coadministration of cordyceps. 3 , 4 Animal experiments suggest a protective role for cordyceps in radiation- and chemotherapy-induced injury, with increased survival times demonstrated in mice. 21 , 22

Cardiovascular effects
Cordyceps has a long history of traditional medicinal use in heart disease. 4 Adenosine and other nucleosides are thought to be responsible for the effects seen in animal studies. 4 A vasodilatory action has been reported in anesthetized dogs, and hypotensive and vaso-relaxant effects have been demonstrated in rats. Reduced heart rate and restoration from arrhythmias have also been shown in animals. 2 , 8 Long-term, open-label clinical studies in cardiac failure have described cordyceps’ effect in improving cardiac function, arrhythmias, and overall quality of life, but are yet to be substantiated by large, high-quality clinical trials. 2 , 4 , 23

Fibrinolytic action of a cordyceps extract has been shown in vitro on bovine and human serum. 24 Platelet aggregation has been inhibited in rabbits and in human platelets in vitro. 8 , 25

A positive effect on hyperlipidemia has also been reported in aqueous extracts of cordyceps. 2 , 4 , 26

Diabetes
Animal studies suggest cordyceps, particularly the polysaccharide extracts, decreases blood glucose levels by improving glucose metabolism and enhancing insulin sensitivity. 3 , 8 , 27 , 28 , 29 , 30 , 31 , 32 Few clinical trials exist; however, 1 small (N = 20), randomized trial found that taking C. sinensis 3 g daily improved the blood sugar profile over placebo. 4

Hepatic function
Hepatoprotective effects of cordyceps extracts have been demonstrated in animal models. 8 , 33 Open-label clinical studies conducted in patients with active hepatitis and posthepatic cirrhosis reported improvements in liver function tests. 4 , 5 , 8

Immune system and anti-inflammatory effects
Aside from limited data from clinical studies conducted in renal transplant recipients and chronic hepatitis patients, 5 , 8 , 34 , 35 the majority of studies have been conducted in vitro and in vivo using mice or rats and were directed at elucidating the mechanism of action for observed effects on the immune system. 4 , 5 , 8 Different fractions of cordyceps extracts (either aqueous or ethanol based) appear to have different effects and, therefore, an immune-modulator function for cordyceps has been proposed. 36 , 37 , 38 , 39 The effects of cordycepin and cordysinocan have been similarly evaluated. 40 , 41

In vitro effects include enhanced phagocytosis activity of macrophages, increased enzymatic activity of acid phosphatase, and induction of interleukin and tumor necrosis factor production. 36 , 37 , 38 , 40 , 41 , 42 , 43 A decrease in cyclooxygenase-2 expression has also been demonstrated in vitro, but potential anti-inflammatory action has not been studied. 5 , 8 , 44

In mice, enhanced splenocyte proliferation, increased plasma corticosterone, decreased production of immunoglobulin E, and modulation of cytokine and CD4+ and CD8+ cell production were reported. 39 , 41 , 45 , 46 , 47 , 48 Increased survival of cardiac grafts, 39 suppression of the effects of streptococcal toxin on phagocytosis, 36 increased survival from streptococcal group A infection, 49 and attenuated disease severity in lupus-prone autoimmune mice were also described. 50 Safety of cordyceps consumption with relation to the immune system was evaluated in mice, with an upregulation of the immune response demonstrated in the absence of splenomegaly. 51

Physical performance
Tests in animals, such as the mouse swim test, generally showed increased time to exhaustion. Unpublished data on studies in elderly volunteers revealed increased energy levels and oxygen-carrying capacity following 6 weeks of cordyceps treatment over placebo. 2 , 4 However, small, randomized, double-blind clinical trials in healthy volunteers and in athletes reported no effect on aerobic capacity, endurance, or performance. In 3 of these clinical trials, cordyceps was used in conjunction with yohimbe or Rhodiola rosea extracts, but no difference over placebo was found. 52 , 53 , 54 In another clinical trial, cordyceps 3.15 g (as Cs-4) taken daily for 5 weeks had no effect compared with placebo. 55

Renal function
Most clinical studies evaluating the effect of cordyceps on renal function are of poor methodology or use cordyceps in combination with other preparations. 9 Clinical studies among elderly patients with long-term renal failure suggest improved renal function as demonstrated by increases in creatinine clearance, and decreases in blood urea nitrogen and serum creatinine. 4 , 5 , 9 These findings are supported by histological studies in animals. 5 , 8 , 9 , 56

In patients in whom cordyceps was coadministered with amikacin and gentamicin, less nephrotoxicity was observed. 5 , 9 In transplantation recipients, the incidence of nephrotoxicity was lower among cordyceps-treated patients, thus allowing for higher cyclosporin A dosing. 5 , 9 , 57

Respiratory effects
In vitro studies suggest aqueous extracts of C. sinensis have a stimulatory effect on ion transport in human airway epithelial cells, possibly because of cordycepin and adenosine. 58 Animal studies suggest the observed effects on respiration are caused by enhanced oxygen utilization capacity, supporting the traditional use of cordyceps in Tibet and Nepal to offset altitude sickness. 4 , 5 Clinical studies conducted in asthma, chronic obstructive pulmonary disease, and bronchitis have suggested efficacy for cordyceps. 4 , 5 The methodology of these clinical studies is, however, not reported or is of open-label design, and cordyceps is often administered in combination with other preparations, making definitive statements about efficacy difficult.

Sexual dysfunction
Experiments in castrated rats showed a mild effect on sexual function. Decreases in erection and mount latency were demonstrated, but no effect on ejaculation latency was found; 59 however, action on steroidogenesis and testosterone have been shown. 60 , 61 , 62 , 63 In clinical studies in elderly populations, improved sexual drive and virility were reported. 2 , 4

Other effects
Inhibition of osteoclast differentiation in mice has been described. 64 Stimulation of erythropeiesis has been reported, as well as antibacterial, antifungal, and antimicrobial activity. 8

Dosage
Dosing supported by product quality data is unavailable, and many herbal supplements contain varying undefined levels of this product. Cordyceps 3 to 6 g/day has been used in patients with long-term renal failure for periods ranging from days to years. 4 , 5 , 9

Cordyceps 6 g/day (using the preparations XinGanBao and Zhiling ) for 2 months has been used in conjunction with chemotherapy in clinical studies involving lung cancer. 4 , 5

In clinical trials evaluating effect on physical performance, cordyceps 3.15 g (as Cs-4) taken daily for 5 weeks had no effect compared with placebo. 55

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Experiments in mice suggest cordyceps has an effect on plasma testosterone levels. 60 , 61 , 62 , 63 Avoid use.

Interactions
None well documented. Fibrinolytic action of a cordyceps extract has been shown in vitro on bovine and human serum. 24 Platelet aggregation has been inhibited in rabbits and in human platelets in vitro. 8 , 25 The American College of Cardiology Writing Committee on Complementary and Integrative Medicine suggests that a risk of potentiation of anticoagulants and monoamine oxidase inhibitors exists. 65 The potential for potentiation of antiviral and hypoglycemic agents has been theorized. 4

Adverse Reactions
One report of hypersensitivity with use of cordyceps exists. 4 Mild GI discomfort, including diarrhea, dry mouth, and nausea, has been reported in clinical studies. 4 , 5 Two cases of lead poisoning associated with cordyceps have been reported, in which the lead content of the preparations was determined to be particularly high. Plasma lead levels returned to normal upon cessation of product consumption. 7 In a study conducted in children with asthma, a combination preparation containing cordyceps did not affect blood cell counts or renal or liver function tests. 66

Toxicology
Cordyceps is considered to be safe; an oral median lethal dose could not be defined. Doses in mice of 80 g/kg body weight did not cause death. 3 No toxic effects on cell proliferation were demonstrated in mice. 64 Safety of cordyceps consumption in reaction to the immune system was evaluated in mice, with an upregulation of the immune response demonstrated in the absence of splenomegaly. 51 Experiments in mice suggest cordyceps has an effect on plasma testosterone levels. 60 , 61