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10:1 Cordyceps CS-4 (Cordyeps Sinensis) extract
Cordyceps sinensis (Cs-4, SMF Mycelium).
Cordyceps is one of the absolute superstars of the Chinese Tonic Herbal system, an extremely effective and powerful life-enhancing agent. Cordycpes is a rare and precious herb, considered to be a moderately Yang primal essence (Jing) tonic of the highest stature.
Cordyceps is used to strengthen the body and mind at a fundamental level. It is said to be able to increase the “primary motive force for life activities.” Because it contains both Yin and Yang it can be used by anyone safely and over a long period of time. It replenishes Yin Jing, restoring the deep energy expended as a result of excessive exertion, adapting to stress or from aging. Cordyceps is thus one of the primary herbal substances used in tonic herbalism as an anti-aging agent and for the purposes of rejuvenation.
NOTE! most commerial cordyceps (including ours) is from vegetarian sources
Cordyceps is very widely used for the purposes of strengthening the primal Kidney functions, which include sexual functions, brain power, structural integrity and healing ability. It is a very powerful Yang tonic. As a sexual tonic, Cordyceps is considered to be one of the best. It is commonly used for impotence, sexual malaise, frigidity and infertility.
Consistent use of Cordyceps helps to strengthen the skeletal structure, and specifically benefits the lower back region, the knees and ankles. It is used for backache due to injury, fatigue, stress or simple aging.
Cordyceps is also a major Lung tonic. It can be used to strengthen respiratory power in those who require extra energy in order to perform physical work (e.g. labor, sports or exercise) or it can be used by those who suffer from deficiency of Lung power. It is especially beneficial to those who suffer chronic Lung weakness with cough, wheezing or shortness of breath.
Cordyceps is considered in Asia to be a powerful athlete’s tonic. It has no steroidal constituents, but greatly improves performance and muscle building capability.
Cordyceps is highly regarded in China as a tonic for those who are recovering from an illness or an operation, or after giving birth. In these cases, the Cordyceps helps the patient recover their physical power, to improve their appetite, and to protect the body from infection.
Many studies now indicate that Cordyceps can help the body resist a wide range of pathogenic bacteria, fungi and viruses. Cordyceps is used in Asia to help treat fungus and yeast infections, and intensive research is being conducted at dozens of institutions in China and Japan relating to the potential of Cordyceps to treat certain varieties of cancer.
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
Volume 4, Number 3, 1998, pp. 289–303
Mary Ann Liebert, Inc.
The Scientific Rediscovery of an Ancient Chinese Herbal Medicine: Cordyceps sinensis
Part I JIA-SHI ZHU, M.D., Ph.D.,(1,2)
GEORGES M. HALPERN, M.D., Ph.D.,(3) and KENNETH JONES (4)
(1) Department of Pediatrics, Stanford University School of Medicine,Stanford, California.
(2) Zhi Dao Tower, 12th floor, Shanghai Medical University, Shanghai, China.
(3) Emeritus, University of California, Davis, California.
(4) Armana Research, Inc., Gibsons, British Columbia, Canada.
This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal.
Cordyceps (Cordyceps sinensis [Berk.] Sacc.), also known as Chinese caterpillar fungus or “DongChongXiaCao” (summer-plant, winter-worm), is one of the most valued Chinese medicinal herbs (Figs. 1 and 2). It was initially recorded in Ben-Cao-Cong-Xin (New Compilation of Materia Medica) by Wu-Yiluo during the Qing Dynasty (1757 ao). According to traditional Chinese medicine (TCM), Cordyceps goes to the “Lung” meridian and the “Kidney” meridian (see below) and provides “lung protection,’ “kidney improvement,” and “Yin Yang double invigoration.”
THE “KIDNEY” AND “LUNG” IN TCM
Although we are not practitioners of TCM,we have included brief explanations of some of the organ concepts mentioned in this review that, however, archaic
to those of us trained in Western physiology and pathology, were and continue to be applied in traditional prescriptions of Cordyceps. The kidneys are
known as “the root of life” in TCM, for they store ‘Jing,’ a substance described as an undifferentiated, prime organic material that is neither yin nor yang and is “the source of reproduction, development, and maturation” (Kaptchuk, 1983). Author and practitioner Ted J. Kaptchuk, O.M.D., in his now classic Western book on TCM, The Web that has no Weaver:
Understanding Chinese Medicine, explains the role of the kidneys and the jing as follows:
Conception is made possible by the power of Jing; growth to maturity is the blossoming of Jing; and the decline into old age reflects the
weakening of Jing. As time passes, the Jing decreases in both vitality and quantity. Because the Kidneys store Jing, all these processes are
governed by the Kidneys. Therefore, reproductive problems such as sterility or impotence and developmental disorders like retarded growth or lack
of sexual maturation are seen as dysfunction of the Kidney’s storing of Jing (Kaptchuk, 1983).
Further to the kidneys, Kaptchuk relates that in TCM the understanding is that they have rulership over the bones and produce the bone marrow. And although the lungs are the administrators of respiration, “normal breathing also requires assistance from the Kidneys.” Here, Kaptchuk enters the subject of Qi or chi, the fundamental “energy of life” that the ancients differentiated into different forms, Kaptchuk writes,
The Kidneys enable the Natural Air Qi to penetrate deeply, completing the inhalation process by what is called “grasping the Qi.”
The Kidneys are thus the root of Qi,’ while the Lungs are the “foundation of Qi.” Proper breathing thus depends on the Kidneys; and Kidney
disharmonies may result in respiratory problems, especially chronic asthma” (Kaptchuk, 1983).
The other meridian that Cordyceps is said to “go to” in TCM is that of the “Lung.” The lungs are said to regulate “the Qi of the entire body” and to rule the Qi (Kaptchuk, 1983).” Kaptchuk explains:
The Lungs take in the Natural Air Qi, propelling it downward by their descending property. This is inhalation. The disseminating property, which “makes things go ’round,’” allows for exhalation, the expulsion of “impure” air. When the lungs are healthy, the Qi enters and leaves smoothly, and respiration is even and regular. When an imbalance or obstruction interferes with the Lungs, impairing either the descending or the disseminating functions, symptoms such as cough, dyspnea, asthma, or chest distention may result (Kaptchuk, 1983).
When there is a “disharmony of the Lungs,” it is said that stagnant Qi or deficient Qi can result in any area of the body. And if the Qi of the lungs is found to be weak, sweat may be found either insufficient or too profuse and the power of resistance of the “Protective Qi will be poor.” Kaptchuk (1983) writes that the “throat is said
to be the ‘door’ of the Lungs and the ‘home’ of the vocal chords, so both the throat and vocal chords are also related to the Lungs. Many common nose and throat disor- ders are therefore treated through the Lungs.”
For centuries, the fruit body and attached mycelium of Cordyceps have been the herb of choice in China to treat “lung” and “kidney” asthenia syndromes (TCM terms describing groups of symptoms associated with respiratory and renal diseases and other disease con- ditions) (Table 1). They have been included as a dietary supplement to maintain health and prevent disease (Table 2) (Jiang, 1993; 1994). In the West, Cordyceps only recently received attention after Chinese female runners established several world long-distance records (1500 to 10,000 meters) within a short period of time in 1993. The athletes’ coach attributed their success in part to a special Cordyceps-containing diet that enhanced their physical performance and endurance (Ma, 1997).
Table 1. Medicinal Uses of Cordyceps
Male and Female Hyposexualities, including Impotence
Asthenia after Severe Illness
Renal Disfunction and Renal Failure
Arrhythmias and other Heart Disease
NOTE: See references in corresponding sections of review, parts 1 and 2.
Cordyceps is a unique black, blade- shaped fungus found primarily at high altitude on the Qinghai-Tibetan plateau. The fungus is parasitic, growing on and deriving nutrients from several species of caterpillar, although primarily that of the moth Hepialus armoricanus Oberthur, which lives 6 inches underground (Chen and Jin, 1992; Yin and Tang, 1995). In late autumn, chemicals on the skin of the caterpillars interact with the fungal spores and release the fungal mycelia, which then infect the caterpillar.
By early summer of the following year, the fungal infestation has killed the caterpillar and the fruiting body can be seen protruding from the caterpillar’s head. This wild form, Cordyceps sinensis, is harvested, whereas the principal fungal mycelium of Cordyceps sinensis, known as Paecilomyces hepiali Chen, is cultivated aseptically (Yue et al., 1995).
Because natural Cordyceps (wild Cordyceps sinensis) is rare, Chinese scientists have extsively examined its lite cycle with the aim of developing a technique for isolating fermentable stratus of Cordyceps sinensis. At the Institute of Materia Medica, Chinese Academy of Medical Sciences, one result of this research has been the isolation of the strain Cs-4 from wild Cordyceps sinensis (Berk.) Sacc. Cs-4 has been used to produce a fermented product of the mycelia of Paecilomyces hepiali Chen and contains pharmacologically active components similar to those of the natural Cordyceps. Since its successful isolation in 1982, the
Cs4 fermentation product has been studied intensively in China. Industrial fermentation methodology (resulting m a commercial product, JinShuiBao
capsule). Chemical composition, therapeutic functions, and toxicity have been thoroughly investigated, and basic research in animals has carried
out. JinShuiBao capsule, the Cs-4 fermentation product, has received approval by the National New Drug Review and Approval committee of the Chinese Ministry. of Public Health, and has been used in clinics throughout China for the indications listed in Table 1.
TABLE 2. DIETARY USES OF CORDYCEPS IN MEDICINAL DISHES
Cooked with hen
Cooked with black-bone hen
Cooked with lean pork
Cooked with sparrow
Cooked with quail
Cooked with steamed turtle
Cooked with baked abalone
Data adapted from Jiang (1984)
In total, more than 2000 patients with various medical disorders have been revolved in clinical trials of Cs-4 in China. The results of these clinical studies (blinded or open- labeled) indicate that Cs-4 is very effective and safe, and very similar to the parental, natural Cordyceps in the amelioration of conditions, with only few and mild side effects. Besides Cs-4, several mycelial strains have been isolated from natural
Cordyceps and some of them are manufactured with fermentation technology (Yin and Tang, 1995). For instance, sinensis (or Cephalosporium donqchongxiacao), a nonsexual phase strain of Cordyceps known as NingXinBao, XinGanBao, and other names, was isolated by the QingHai Institute of Livestock and
Veterinary Sciences. Cn80-2 (Paecilomyces sinensis), another nonsexual phase strain, was isolated by FuJian QingLiu County Hospital and Institute of Microbiology, Chinese Academy of Sciences. SMIH8819 is a product of Sanming Mycological Institute, Fujian, China. 832 (Scydalilum sp.) was isolated by the Navy Institute of Medicine. Hirsutella sinensis, Mortierella hepiali Chen lu sp. nov., Scytalidium hepiali G. L. Lisp. nov., Tolypocladimn sinensis C.I. sp. nov., and others have been isolated natural Cordyceps (Yin and Tang, 1995). The Latin binomials given for the derivative fungi describe imperfect fruit bodies generated when the various mycelia were allowed to grow out. Although derived from the fruit body of Cordyceps sinensis, they are characteristically enough from the parent fungus, to
be taxonomically separate; hence the term fungi imperfecti (Alexopoulos, 1962)
SEVEN CLASSES OF CHEMICAL CONSTITUANTS OF
1. Proteins, peptides, all essential amino acids, and polyamines. In addition to ail the essential amino acids, Cordyceps contains uncommon cyclic dipeptides including cyclo-(Gly-Pro), cyclo-(Leu-Pro), cyclo-(Val-Pro), cyclo-(Ala-Leu), cyclo-(Ala-Val), and cyclo-(Thr-Leu). Small amounts of polyamines, including 1,3-diamino propane, cadaverine, spermidine, spermine, and putrescine, have been identified.
Saccharides and sugar derivatives (eg, d-mannitol) were identified and their pharmacological activity has been reported. A group of interesting oligosaccharides and polysaccharides (Cs-l) isolated from natural Cordyceps stimulate macrophage function, and promote lymphocyte transformation. A bioactive 23-kd-protein-bound polysaccharide was shown to consist mainly of mannose and galactose in a ratio of 3 to 5, and protein.
Sterols, including ergosterol, Delta-3 ergosterol, ergosterol peroxide,/3-sitosterol, daucosterol, and campasterol.
Eleven nucleoside compounds have been found in natural Cordyceps. The major nucleosides in C. sinensis include adenine, uracil, uridine, guanosine,
thymidine, and deoxyuridine.
Fatty, acids and other organic acids. Twenty-eight saturated and unsaturated fatty acids and their derivatives have been isolated from C. sinensis. Polar compounds of natural Cordyceps extracts and Cs-4 include many compounds of hydrocarbons, alcohol, and aldehyde.
Vitamins, including vitamins Bi, B2, B12, E, and K.
7. lnorganics, including K, Na, Ca, Mg, Fe, Cu, Mn, Zn, Pi, Se, Al, Si, Ni, Sr, Ti, Cr, Ga, V, and Zr.
Data from Guo, 1986; Huang et al., 1991; Tao, 1995; Xia et al., 1985; Xu, 1992; Yue et al., 1995; Zhu and Xinjingsheng,
Table 3 lists seven classes of chemical constituents found in natural Cordyceps sinensis and its mycelial fermentation products (Guo, 1986; Huang et al., 1991; Tao, lt295; Xia et al., 1985; Xu, 1992; Yue et al., 1995: Zhu, 1993). Pharmacologically active components of Cordyceps sinensis are still incompletely understood. Cordycepin and cordycepic acid were identified initially in Cordyceps militaris by Cunning- ham et al. (1951) and considered as the active components Later, scientists confirmed that cordycepic acid was in fact d-mannitol. As for cordycepin (3′-deoxyadenosine), its existence in C. sinensis has long been controversial.
Although many laboratories failed to confirm its presence in this species, a recent study reported characterization of cordycepin and 2′-deoxyadenosine in an extract preparation of C. sinensis by use of nuclear magnetic resonance (NMR) and infrared spectroscopy (IR) techniques (Chen and Chu, 1996). In addition, other components, such as adenosine, saccharides, and minor elements, were for many years believed to probably play certain roles in the pharmacology of C. sinensis. In TCM, Cordyceps has been used to treat a wide range of conditions, including respira-ton’, renal, liver,
and cardiovascular diseases, hyposexuality, and hyperlipidemia (Table 1). Cordyceps has also been used to modulate the immune system and as
an adjuvant in cancer therapy. Yet only in comparatively recent times have the medicinal effects of Cordyceps been tested in controlled clinical trials, predominantly in China. In reviewing the results of these studies, where appropriate, we have included animal studies that assist in elucidating the mechanisms of activity involved.
Improvement of Physical Performance and Quality of Life
The preparation and use of Cordyceps as a tonic beverage, although centuries old, was only given greater attention during the last 20 years in China.
The recent success of Chinese runners on a special Cordyceps-containing diet brought greater scientific attention to bear on the potential of the mycelia from Cs-4 to improve physical performance and quality of life. The question researchers are now attempting to answer is whether the putatively enhanced physical endurance attributed to Cordyceps can be supported on a strictly scientific basis.
Preclinical animal studies. The effects of Cordyceps extracts on the energy state of mouse liver were examined using in vivo serial 3]p NMR spectroscopy.
After mice were given water extracts of Cs-4 (0.2 or 0.4 g/kg) orally for 7 days, the ratio of adenosine triphosphate (ATP): inorganic phosphate (Pi) in the liver was significantly increased by an average of 45% to 55%, as compared with the placebo control group (both p < 0.001 ) (Xu CF, Bao TI’, He CH, Zhu JS, Chang J, manuscript in preparation). The elevated ATP:Pi ratios returned to the baseline levels 7 days after Cs-4 treatment was discontinued. Similarly, during a 3-week intra- gastric treatment of mice with water extracts of another mycelial fermentation product, SMIH8819 (0.2 g/kg per day), there was a consistent increase in the ratio of ATP:Pi in the liver (Manabe et al., 1996). This increase, observed after 1 week of treatment, was maintained throughout the study and was significantly greater than that of control groups.
In addition to the promotion of higher bioenergy levels by Cordyceps, researchers examined oxygen consumption by mice and their ability to survive after
Cs-4 therapy in a hypoxic environment, to elucidate the effects of Cs-4 on oxygen utilization efficiency (Lou et al.,1986). Under conditions of stimulation of oxygen consumption by a subcutaneous injection of isoprenaline (300 ,ug/kg), Cs-4 extract (equivalent to crude Cs- 4, 5 g/kg, J.p., or 10g/kg, i.g.) significantly reduced oxygen consumption by the mice by 41% to 49% within 10 minutes and by 30% to 36% in the second 10 minutes, as compared with controls (all p <0.001) (Lou et al., 1986). In a low-oxygen environment, the mice lived 2 to 3 times longer after the Cs-4 treatment (all p < 0.001). The Cs-4- induced reduction of oxygen consumption and the prolonged survival of treated animals in a hypoxic environment indicated a more efficient use of oxygen to support essential physiological activities of organs/tissues and greater tolerance to hypoxia-induced acidosis than that of the controls.
A more vigorous study was conducted using an in vivo mouse model of epinephrine- inducedacute pulmonary edema, which causes systemic anoxia, acidosis,
and death (Wan and Zhang, 1985). It was noted that mice treated with Cs-4 (6 g/kg, J.g.) had a significantly greater survival rate: 20% mortality
at 30 min- utes after epinephrine treatment compared with 80% mortality in the control group (p =0.011); 60% mortality at 60 and 90 minutes after epinephrine treatment compared with 100% mortality in the control group (p = 0.043).
These results suggest that natural Cordyceps and its mycelial fermentation products may improve bioenergetic status by improving an internal balance mechanism
by which test animals are able to make more efficient utilization of oxygen under economy of energy consumption. This effect may allow animals to manage efficiently inadequate oxygen supply and a basic energy requirement for essential physiological activities, and to promote greater tolerance to hypoxia-induced acidosis than controls. Whether these properties may to some extent account for the apparent overall enhancement of physical capability and endurance and antifatigue effects found in humans using natural Cordyceps, or its fermentation products as a dietary supplement, is currently the focus of of ongoing multidisciplinary research at various centers in China.
Clinical studies: Placebo-controlled clinical studies examined the effects of Cs-4 therapy in elderly patients with fatigue and other senescence-related symptoms (Cao and Wen, 1993; Zhang et al., 1995). Compared with no improvement in symptoms in the placebo-treated patients, most of the Cs-4-treated
patients reported overall clinical improvement (Zhang et al., 1995). The subjective improvements included alleviation of fatigue, cold intolerance, dizziness, frequent nocturia, tinnitus, hyposexuality, and amnesia (Table 4).
TABLE 4. CLINICAL EFFECTS OF Cs-4 ON SENESCENCE
Intolerance to cold
Elderly people with symptoms of senescence were enrolled in a double-blind trial and treated with either Cs-4 or placebo (3 g/day) for 3 months. Note: n = number of patients with the symptom prior to the treatment. Results are expressed as percentage of patients who experienced clinical improvement. Data are adapted from Zhang et al. (1995).
Cordyceps Article Part I, Page 2-
Covers effects on Heart, Kidney, Liver, Endocrine and Sexual Performance
Another active-herb (seed oil of mujingyou, Vitex negundo var.heterophylla) - controlled clinical study found that after receiving Cs-4 treatment for 1 month, patients with respiratory diseases felt physically stronger; some of them were able to jog for 20 meters (Institute of Materia Medica, Beijing, China, unpublished report). The Cs-4 treatment appeared to be highly efficacious with a total effective rate of 82.9%, as compared with 40.2% for the active control group (p < 0.01).
A study on the long-term use of Cs-4 in combination with standard therapy in patients with chronic heart failure was the subject of a study in China in patients on digoxin, hydrochlorothiazide, isosorbide dinitrate, furosemide, lanatoside, dopamine, and dobutamine (Chen, 1995). Long term administration of Cs-4 as an adjuvant treatment in patients with congestive heart failure gave rise to significantly greater improvements in quality of life than reportedby disease- and age-matched control patients who received only standard drug treatments for congestive heart failure. Quality of life parameters included improvements of general physical condition, mental health, sexual drive, and cardiac function (Table 5).
The enhancement of physical performance and amelioration of quality of life in response to Cs-4 treatment may be attributed to the improvement of energy states with greater efficiency of oxygen utilization described earlier, as well as to the function improvement in oxygen scavenging and in pulmonary, cardiovascular, and other systems, as detailed below, or in part II of this review.
TABLE 5. IMPROVEMENT OF QUALITY OF LIFE OF PATIENTS WITH CHRONIC
HEART FAILURE IN RESPONSE TO LONG-TERM CS.-4 ADJUVANT TREATMENT
Shortness of breath / Fatigue index
General physical condition
Patients with chronic heart failure were treated with Cs-4 (3-4 g/day) for 26 ± 3 months, in addition to standard drug
treatments for congestive heart failure. Data are adapted from Chen (1995) and are expressed as fractions of mean values observed for controls who received only standard therapies without Cs4 adjuvant treatment. Shortness of breath/fatigue index was assessed according to Yale grading system; general physical condition according to Feistein method; emotional-psychological condition according to Croog method; and sexuality of patients was based on a modified Kong questionnaire. note: n.s., not significant compared with pretreatment values.
Antisenescence and oxygen-free radical scavenging activity
The use of natural Cordyceps to ameliorate conditions associated with aging and senescence is centuries old. Yet scientific research of its potential in geriatrics has only recently been initiated. There is evidence to show that during aging in humans and animals, a considerable accumulation of an excess of oxygen-free radicals occurs, which results in oxidative damage to cells and their intracellular organelles, including age- and illness-associated damage to the energy-producing mitochondria. As one mechanism, an aging- or disease-related dramatic reduction in the oxygen free radical-scavenging activity of superoxide dismutase (SOD) is believed to be responsible for excessive cellular oxidative damage. The antisenescence effects of Cordyceps in relation to an ability to activate SOD and scavenge oxygen free radicals were studied in humans and animals.
In placebo-controlled clinical trials (Cao and Wen, 1993; Zhang et al., 1995), Cs-4 was administered orally to elderly patients with asthenia. In association with the majority showing subjective improvement (as shown in Table 4), there was a concomitant significant increase in red blood cell (RBC) SOD activity in the Cs-4-treated patients (Table 6), which was significantly better than that of the placebo group. Associated with the increases of SOD, concentrations of plasma malondialdehyde (MDA, a measure of lipoperoxide, an oxygen free-radical species) were significantly decreased in Cs-4-treated elderly patients, whereas there was no significant change in the control group. As also demonstrated in this study (Table 6), even with age-associated low pretreatment SOD activity and high MDA concentrations in the el
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