Cordyceps
Scientific Name(s): Cordyceps sinensis (Berk.) Sacc. Family: Clavicipitaceae
Common Name(s): Cordyceps , Chinese caterpillar fungus , Cs-4 , Dong Chong Xia Cao , 1 , 2 semitake
Clinical Overview
Uses of Cordyceps
Affects numerous human body systems, including the circulatory, respiratory, and immune systems, as well as the liver, kidneys, and sex organs. Cordyceps has been used as an adjuvant in cancer therapy.
Cordyceps Dosing
Accurate dosing is not available. Many herbal supplements on the market contain varying undefined levels of this product.
Contraindications
Contraindications have not yet been identified.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
Cordyceps Interactions
None well documented.
Cordyceps Adverse Reactions
Mild GI discomfort (including nausea, upset stomach, and dry mouth).
Toxicology
Cordyceps is considered to be very safe and an oral LD50 (median lethal dose) could not be defined. Doses in mice of 80 g/kg body weight did not cause death. One study indicated that Cordyceps is not mutagenic or teratogenic. There are reports from clinical studies of mild GI discomfort (including nausea, upset stomach, and dry mouth). In another report, some patients taking Cs-4 developed a systemic allergic reaction. 3
Botany
C. sinensis is a black, blade-shaped fungus found primarily in the high altitudes on the Tibetan plateau in China. Wild cordyceps is rare. This mushroom is parasitic and grows on and derives its nutrients from moth caterpillars. In the fall, the fungal mycelia infect the caterpillar. The fungal infestation kills the caterpillar by early summer of the following year, thus releasing the fruiting body. The wild form of C. sinensis is harvested, while the principal fungal mycelium ( Paecilomyces hepiali Chen) is cultivated aseptically. 2
History
The fruiting body and attached mycelium of cordyceps has been used in Chinese culture for centuries. In traditional Chinese medicine, it is valued for its activity in restoring energy, promoting longevity, and improving quality of life. C. sinensis affects numerous human body systems including the circulatory, respiratory, and immune systems, as well as the liver, kidneys, and sex organs. Cordyceps has been used as an adjuvant in cancer therapy. 2 , 3 , 4
Chemistry
Seven classes of natural chemical constituents are found in wild C. sinensis including proteins, peptides, all essential amino acids, and polyamines; saccharides and sugar derivatives; sterols; nucleosides (including adenine, uracil, uridine, guanosine, thymidine, and deoxyuridine); fatty acids and other organic acids; vitamins (including B 1 , B 2 , B 12 , E, and K); and inorganic elements. 2 , 5 Cordycepin and other adenosine derivatives, mannitol, several unique sterols and their glycosides, polysaccharides, and cyclic peptides have been identified. 6
Cordyceps Uses and Pharmacology
Over 2000 patients with various medical disorders have been involved in clinical trials using Cs-4 in China. Cs-4 is a strain of the wild C. sinensis and has been studied extensively in China. The chemical and pharmacological profiles are similar to natural C. sinensis and most of the research available was completed using Cs-4.
In traditional Chinese medicine, C. sinensis has been used to treat male impotence and other types of sexual dysfunction. Numerous animal studies and clinical trials have studied the effects of C. sinensis on sexual function.
In both animal and human clinical studies, C. sinensis has shown renal protective effects against nephrotoxicity of aminoglycosides and cyclosporin A.
C. sinensis also has demonstrated hepatoprotective effects in an animal study 7 and in clinical trials.
A hypoglycemic effect has been documented in animal studies. 8 , 9 , 10
Investigators also have reported enhanced immune system activity in animal and in vitro studies with C. sinensis .
Cordyceps has been used as an adjunct in cancer treatment and appears to improve tolerance to the adverse effects associated with radiation and chemotherapy.
The anti-inflammatory properties of cordyceps also have been reviewed; however, the mechanism of action has yet to be elucidated. 3
Sexual dysfunctionClinical data
In several placebo-controlled, double-blind studies, patients with reduced sexual drive are typically treated with Cs-4 (3 g/day) for approximately 2 months. In elderly patients, clinical improvement of sexual drive and function for the Cs-4 group was statistically significant as compared with the control group. There was an increase in 24-hour urine 17-ketosteroids in the Cs-4-treated patients; thus Cs-4 may affect sexual drive through the sex hormone systems or through a direct action on the sexual center of the brain and sexual organs. 2 , 11 , 12
HyperlipidemiaClinical data
Cs-4 also has been used in the treatment of hyperlipidemia and may have a hypocholesterolemic effect. 2 , 13 In a double-blind, placebo-controlled clinical trial involving 273 patients, the Cs-4 group had a reduction in triglycerides after only 1 month of treatment. Overall, half of the patients on Cs-4 therapy (3 g/day) had reductions in total cholesterol and triglycerides, and a significant increase in high-density lipoprotein. 2
AgingClinical data
In a double-blind, placebo-controlled trial, elderly patients with senescence-related symptoms had significant improvements in tolerance to cold ( P < 0.001), fatigue ( P < 0.001), dizziness ( P < 0.001), tinnitus ( P = 0.001), frequent nocturia ( P = 0.004), hyposexuality ( P = 0.05), and amnesia ( P = 0.003). Patients were randomly assigned and received either Cs-4 (3 g/day) or placebo for 3 months. There was a concurrent increase in red blood cell superoxide dismutase (SOD) activity ( P < 0.001). Reduction in SOD is recognized as one of the factors related to aging and may lead to accumulation of excessive oxygen-free radicals and oxidative damage to cells. 2
ArrhythmiasClinical data
In a 3-month, open-label clinical trial, Cs-4 was used to treat 38 elderly patients with various arrhythmias. The investigators concluded that Cs-4 was effective in treating patients with tachyarrhythmia and bradyarrhythmia, and the longer the therapy duration, the better the clinical improvement. The majority of patients with supraventricular arrhythmias experienced partial to complete recovery in the electrocardiograms. 3 , 14
Heart failureClinical data
A 26-month trial using Cs-4 (3 to 4 g/day) in combination with standard therapy (digoxin, hydrochlorothiazide, isosorbide dinitrate, furosemide, lanatoside, dopamine, and dobutamine) was studied in 64 chronic heart failure patients. Patients using Cs-4 as an adjuvant treatment reported improvement in general physical, emotional, and psychological well-being as compared with controls. There were no statistically significant differences in mortality between the two groups. Overall, patients taking Cs-4 had statistically significant improvements in the shortness of breath/fatigue index ( P < 0.01), general physical condition ( P < 0.05), emotional-psychological condition ( P < 0.05), and sexual drive ( P < 0.001) as compared with controls. 2
Chronic obstructive pulmonary diseaseClinical data
In an open-label, clinical trial, patients with chronic obstructive pulmonary disease reported improvements in cough, phlegm, appetite, vitality, and pulmonary symptoms after treatment with Cs-4 (3 g/day for 3 weeks) compared with controls. There was a significant increase in SOD activity ( P < 0.001) compared with baseline. In another open-label, clinical trial, patients with chronic renal dysfunction also had significant increases in SOD activity ( P < 0.001) compared with pretreatment levels after treatment with Cs-4 (5 g/day for 4 weeks). 2
RespiratoryClinical data
More than 5 clinical studies (all approximately 4 weeks in duration) demonstrated significant clinical improvements ( P < 0.01) in respiratory symptoms (including chronic bronchitis, bronchial asthma, and cor pulmonale) after administration of a cordyceps-containing medication. Dosages ranged from 3 to 4.5 g/day of Cs-4 for 2 to 12 weeks. When Cs-4 was used in combination with oxygen and other drugs in treating patients with cor pulmonale (right-sided heart failure), improvements were seen in respiratory and heart function as well as in sleep and emotional-spiritual state. The combined use of Cs-4 (3 g/day) with astemizole (10 mg/day) and ketotifen (2 mg/day) was effective in treatment of asthma as compared with the controls treated with Western medicine alone ( P < 0.05). A potential mechanism may involve Cs-4 reducing the production of IgE (which will reduce the asthma attack) through T H1 and T H2 immune responses. 3 , 15
Renal functionClinical data
C. sinensis may improve kidney function and have renal protective effects against nephrotoxic chemicals. Cs-4 (6 g/day for 30 days) was effective in improving renal function in 30 patients with chronic renal failure. Compared with pretreatment levels (not necessarily a valid reference point), investigators reported significant improvement in serum creatinine ( P < 0.02), red blood cell count ( P < 0.05), anemia ( P < 0.02), creatinine clearance ( P < 0.001), and blood urea nitrogen ( P < 0.01). Another study found similar significant improvements as well as reduction in urinary protein ( P < 0.01). Results from other studies suggest improvement of renal function by C. sinensis linked with involvement of T-cell-mediated immune functions. In one study, elderly patients (53 to 73 years of age) with no history of renal disease were treated IM or IV with amikacin (0.4 g/day for 6 days) with either placebo or C. sinensis (6 g/day for 7 days) for the treatment of an acute infection. After the therapy, the accumulated 24-hour urinary N-acetyl-beta-D-glucosaminidase (NAG) level was increased by 4 times in controls compared with double in those patients receiving C. sinensis ( P < 0.05). NAG is an index for aminoglycoside-induced renal damage. 3 , 16
HepatitisClinical data
In a 3-month, open-label trial of 33 patients, a cultivated mycelial product of C. sinensis was effective in the treatment of chronic active hepatitis B. Investigators reported after the treatment that the thymol turbidity test (TTT) and serum glutamic-pyruvic transaminase (SGPT) either improved or returned to normal. In addition, serum albumin increased and gamma globulin decreased significantly. No significant changes were seen in TTT or ALT in another study of 22 patients with hepatic cirrhosis; although significant improvements were seen in serum albumin ( P < 0.01) and gamma globulin ( P < 0.05). Other references referred to in this report have shown similar results. 3
DiabetesClinical data
In a randomized trial involving 42 patients with diabetes, Cs-4 (3 g/day for 30 days) was found to be an effective treatment in combination with traditional Chinese herbs compared with a control group given only the herbs. Patients in the treatment group previously had a positive urinary protein test; after treatment, half of these patients tested negative compared with no change in the controls. 3
Leukemia and immunocompetent patientsClinical data
One study demonstrated enhanced activity of natural killer (NK) cells in patients with leukemia and in immunocompetent individuals. It also prevented reductions in NK cell activity in immunosuppressed mice. 3
Lung cancerClinical data
In 59 patients with terminal lung cancer, administration of Cs-4 (2 to 3 g/day) resulted in more patients completing radiation and/or chemotherapy compared with a control group ( P < 0.01). Cs-4 also may minimize bone marrow impairment because patients in the Cs-4 treatment group had normal blood counts as compared with the control group ( P < 0.01). One study concluded that the fruiting body of C. sinensis contains growth inhibitors against tumor cells. 3 , 6
Animal dataInvestigators studied the effect of a fraction of mycelia of C. sinensis (150 mg/kg/day) for its antifatigue and antistress effects against a stimulus (swimming endurance capacity) in vivo using rats and mice. The researchers concluded the fraction of mycelia of C. sinensis has antifatigue and antistress effects on the following stress indices: serum level measurements of total cholesterol, lactate dehydrogenase, alkaline phosphatase, aspartate transaminase, and alanine transaminase. 12 , 17
Investigators have reported the following pharmacological activities of natural C. sinensis on the cardiovascular system in animal studies in vivo or with isolated organs: Dilation of arteries and improvement of nutritional blood supply to organs and extremities; reduction of heart rate; antiarrhythmic effects; effects against acute myocardial ischemia and stress-induced myocardial infarction; and effects of thrombosis and anti-aggregation of platelets.
Dosage
Accurate dosing is not available. Many herbal supplements on the market contain varying undefined levels of this product.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
Interactions
None well documented.
Adverse Reactions
Mild GI discomfort (including nausea, upset stomach, and dry mouth).
Toxicology
Cordyceps is considered to be very safe and an oral LD50 (median lethal dose) could not be defined. Doses in mice of 80 g/kg body weight did not cause death. One study indicated that Cordyceps is not mutagenic or teratogenic. There are reports from clinical studies of mild GI discomfort (including nausea, upset stomach, and dry mouth). In another report, some patients taking Cs-4 developed a systemic allergic reaction. 3
Bibliography
1. Huang KC. The Pharmacology of Chinese Herbs . 2nd ed. Boca Raton, FL: CRC Press; 1999.2. Zhu JS, Halpern GM, Jones K. The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis : part I. J Altern Complement Med . 1998;4:289-303.
3. Zhu JS, Halpern GM, Jones K. The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis : part II. J Altern Complement Med . 1998;4:429-457.
4. Stamets P. Novel antimicrobials from mushrooms. HerbalGram . 2002;54:28-33.
5. Huang LF, Liang YZ, Guo FQ, Zhou ZF, Cheng BM. Simultaneous separation and determination of active components in Cordyceps sinensis and Cordyceps militarris by LC/ESI-MS. J Pharm Biomed Anal . 2003;33:1155-1162.
6. Bok JW, Lermer L, Chilton J, Klingeman HG, Towers GH. Antitumor sterols from the mycelia of Cordyceps sinensis . Phytochemistry . 1999;51:891-898.
7. Liu YK, Shen W. Inhibitive effect of Cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism. World J Gastroenterol . 2003;9:529-533.
8. Zhao CS, Yin WT, Wang JY, et al. CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats. J Altern Complement Med . 2002;8:309-314.
9. Balon TW, Jasman AP, Zhu JS. A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J Altern Complement Med . 2002;8:315-323.
10. Hockaday TD. Two herbal preparations, Cordyceps Cs4 and Cogent db: do they act on blood glucose, insulin sensitivity, and diabetes as “viscous dietary fibers?” J Altern Complement Med . 2002;8:403-405.
11. Hsu CC, Tsai SJ, Huang YL, Huang BM. Regulatory mechanism of Cordyceps sinensis mycelium on mouse Leydig cell steroidogenesis. FEBS Lett . 2003;543:140-143.
12. Hsu CC, Huang YL, Tsai SJ, Sheu CC, Huang BM. In vivo and in vitro stimulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells. Life Sci . 2003;73:2127-2136.
13. Koh JH, Kim JM, Chang UJ, Suh HJ. Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis . Biol Pharm Bull . 2003;26:84-87.
14. Chiou WF, Chang PC, Chou CJ, Chen CF. Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis . Life Sci . 2000;66:1369-1376.
15. Kuo YC, Tsai WJ, Wang JY, Chang SC, Lin CY, Shiao MS. Regulation of bronchoalveolar lavage fluids cell function by the immunomodulatory agents from Cordyceps sinensis . Life Sci . 2001:68:1067-1082.
16. Shahed AR, Kim SI, Shoskes DA. Down-regulation of apoptotic and inflammatory genes by Cordyceps sinensis extract in rat kidney following ischemia/reperfusion. Transplant Proc . 2001;33:2986-2987.
17. Koh JH, Kim KM, Kim JM, Song JC, Suh HJ. Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis . Biol Pharm Bull . 2003;26:691-694.
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