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Cordyceps

Lung Health, GlossarySuccess Chemistry Staff

ATP, adenosine triphosphate; GM-CSF, granulocyte

macrophage colony-stimulating factor; GRAS, generally

recognized as safe; HDL, high-density lipoprotein; IFN,

interferon; Ig, immunoglobulin; IL, interleukin; iNOS,

calcium-insensitive nitric oxide synthases; LD50, median

lethal dose; LDL, low-density lipoprotein; NK cell, natural

killer cell; PAH, polyaromatic hydrocarbons; PAMP,

pathogen-associated molecular patterns; TCM, traditional

Chinese medicine; TLR, Toll-like receptor; TNF, tumor

necrosis factor.

INTRODUCTION

 

Species of the genus Cordyceps (Fr.) Link (also known

as Chinese caterpillar fungi, or Tochukaso in Japanese;

Clavicipitaceae, Ascomycetes) are the fungi found growing

on insect larvae, mature insects, or fruiting bodies

of truffles of genus Elaphomyces.

 

Cordyceps has a long history as a rare and exotic medicinal fungus. It has been a

highly regarded cornerstone of Chinese medicine for centuries;

one that reportedly has a number of far reaching

medicinal effects. Most people in the West have only

come to know of Cordyceps within the last twenty years,

during which time, modern scientific methods have been

increasingly applied to the investigation of its seemingly

copious range of medicinal applications, in an attempt

to validate what Chinese practitioners have noted for

centuries (2).

Diversity and Artificial Cultivation

There are currently more than 680 documented species

of Cordyceps, found on all six inhabited continents and in

many climatic zones and habitats, and occurring parasitically

or commensally with a range of hosts

 

Due to the rarity and high prices of the wild collected variety,

attempts have long been made to cultivate C. sinensis. By

the mid 1980s, the majority of C. sinensis available in the

world’s marketplace was artificially cultivated (4).

Many companies now produce artificially cultivated

C. sinensis products, both from the mycelium as well as

from the fruit bodies. The increase in supply has given

rise to variations in purity and quality, creating a situation

in which there are a large number of counterfeit and

adulterated products being sold (3). Recently, there have

been introduced, new methods for assaying the quality of

Cordyceps spp. products (5). The large variations in quality

found in cultivated C. sinensis has lead many consumers

to believe the wild collected variety is medicinally better

than the cultivated type. But with new advances in

biotechnology, this is rapidly changing (6).

Contamination and Adulteration of Cordyceps

As found in its natural state, C. sinensis is attached to the

mummified body of the caterpillar, from which it arose. It

is harvested whole in this way, dried, and supplied into

the market. Because C. sinensis is sold by weight and intact

fruiting bodies fetch higher prices in traditional markets,

collectors have historically inserted a small bit of twig into

many of the caterpillars, resulting in an increase in weight

and the appearance of intact fruiting bodies (5). This is

probably a harmless practice, as long as the object inserted

is from a nontoxic source. However, modern collectors

have inserted lead or other metal in order to boost the

weight, so anyone who chooses to use the wild collected

C. sinensis, rather than the cultivated variety, would be

well advised to break each one of the caterpillars in half

before use, so that any bits of foreign matter can be readily

discerned and removed.

History and Traditional Uses

The first written record of the Cordyceps mushroom comes

from China, in the year AD 620, at the time of the Tang Dynasty,

bringing substance to the once intangible allegorical

narrative, which spoke of a creature, whose annual existence

alluded to a transformation from animal to plant,

in summer, and then again from plant to animal, in winter

(1). Tibetan scholars wrote of the healing animal/plant

through the 15th to 18th centuries, and in 1757, the earliest

objective and scientifically reliable depiction of the Cordyceps

mushroom was written by the authorWu-Yiluo in the

Ben Cao Congxin (“New Compilation of Materia Medica”),

during the Qing Dynasty (2–3).

C. sinensis is found at high altitudes on the Himalayan

Plateau, and thus, is difficult to harvest. Due

to such difficulties, Cordyceps has always been one of the

most expensive medicinal fungi known. Its high price had

relegated it almost exclusively to members of the Emperor’s

court and others among the Chinese nobility, historically

beyond the reach of the average Chinese subject.

Despite its cost and rarity, the unprecedented litany of

medicinal possibilities for Cordyceps spp. has made it a

highly valued staple of the TCM.

The name Cordyceps comes from the Latin words,

cord and ceps, respectively meaning, “club” and “head.”

The Latin word conjunction accurately describes the appearance

of these club fungi, whose stroma and fruit body

Cordyceps sinensis in natural habitat (4550 m in Tibet, China).

extend from the mummified carcasses of insect larvae,

usually that of the Himalayan ghost Moth, Thitarodes armoricanus

(Hepialis armoricanus). In historical and general

usage, the term “Cordyceps” normally refers specifically

to the species C. sinensis. However, the name “Cordyceps”

has come to be used for a number of closely related species

over the last few years, which have been found to be much

easier to cultivate. While C. sinensis may be the most wellknown

species, there are many other species in the genus

Cordyceps, in which modern science may have uncovered

potentially valuable medicinal properties.

The medicinal values of Cordyceps spp. have been

recognized since ancient times in China and the surrounding

Orient; but knowledge of this only reached Western

scientific audiences in 1726, when it was introduced at a

scientific meeting in Paris. The first specimens were carried

back to France by a Jesuit priest, who chronicled his

experiences with the Cordyceps mushroom during his stay

at the Chinese Emperor’s court (1,4).

The range of therapeutic uses claimed for Cordyceps

spp. is far reaching; although most of them have yet to

be sufficiently investigated. In TCM, C. sinensis has been

used to treat conditions including respiration and pulmonary

diseases, renal, liver, and cardiovascular diseases,

hyposexuality, and hyperlipidemia. It is also used in the

treatment of immune disorders and as an adjunct to modern

cancer therapies (chemotherapy, radiation treatment,

and surgery) (1). C. sinensis is believed by many, particularly

in and around Tibet, its place of origin, to be a

remedy for weakness and fatigue; and it is often used as

an overall rejuvenator for increased energy while recovering

from a serious illness. Many also believe it to be a

treatment for impotence, acting as an aphrodisiac in both

men and women. C. sinensis is often prescribed for the

elderly to ease general aches and pains. TCM practitioners

also recommend the regular use of C. sinensis in order

to strengthen the body’s resistance to infections, such as

colds and flu, and to generally improve the homeostasis

of the patient.

CHEMISTRY AND PREPARATION OF PRODUCTS Nutritional Components

Cordyceps spp. contains a broad range of compounds,

which are considered nutritional. C. sinensis contains all

of the essential 18 amino acids. The content of amino

acids after hydrolysis is mostly reported in the range of

20% to 25%. The highest contents are glutamate, arginine,

and aspartic acid, and the major pharmacological components

are arginine, glutamate, tryptophan, and tyrosine

(7). Also found are vitamins E, K, and the water-soluble

vitamins B1, B2, and B12. In addition, Cordyceps spp. contain

many sugars, including mono-, di-, and oligosaccharides,

and many complex polysaccharides, proteins,

sterols, nucleosides, macro- and microelements (K, Na,

Ca, Mg, Fe, Cu, Mn, Zn, Pi, Se, Al, Si, Ni, Sr, Ti, Cr, Ga, V,

and Zr) (2,5).

Polysaccharides

C. sinensis contains a large amount of polysaccharides,

which can be in the range of 3% to 8% of the total weight,

and usually comes from the fruiting bodies, the mycelium

of solid fermentation submerged cultures and the broth

(7). Four -D-glucan exopolysaccharides from C. militaris

with different molecular masses ranging from 50 to

2260 kDa were reported by Kim et al. (8). In the case of

C. sinensis, most of the heteropolysaccharides contained

mannose, galactose, glucose, and mannose in higher levels

with smaller amounts of arabinose, rhamnose, fructose,

and xylose, respectively. The average molecular mass

varies between 7 and 200 kDa. C. militaris polysaccharides

consisted mostly of glucose, galactose, and mannose

with traces of rhamnose and xylose and average molecular

weight approximately 60 kDa (9).

Proteins and Nitrogenous Compounds

Cordyceps spp. contain proteins, peptides, polyamines, all

essential amino acids, some 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, such as 1,3-diamino

propane, cadaverine, spermidine, spermine, and putrescine,

have also been identified (4). Many nucleosides

have been found in Cordyceps spp., including uridine, several

unique deoxyuridines, adenosine, dideoxyadenosine,

hydroxyethyladenosine, cordycepin [3deoxyadenosine],

cordycepin triphosphate, guanidine, deoxyguanidine,

and other altered and deoxygenated nucleosides, many

of which are found nowhere else in nature (Fig. 2). Chen

and Chu (10) found cordycepin and 2-deoxyadenosine in

an extract of C. sinensis.

Sugar-binding proteins named lectins were isolated

from C. militaris. N-terminal amino acid sequence differed

Cordyceps 187

Normal adenosine Cordycepin

Hydroxyethyladenosine Dideoxyadenosine Deoxygenated at the 3' and 2' position

Figure 2 Some of the unique nucleosides found in C. sinensis.

greatly from other lectins (11). Production of the nonribosomal

peptides cicapeptins I and II from C. heteropoda

were reported by Krasnoff et al. (12).

Sterols

A number of sterol-type compounds have been found in

Cordyceps spp.: ergosterol, -3 ergosterol, ergosterol peroxide,

3-sitosterol, daucosterol, and campeasterol, to name

a few (1). Another compound, sterol H1-A was found by

Chen et al. (13) and it was claimed to be effective in the

treatment of autoimmune disorders.

Other Constituents

Twenty-eight saturated and unsaturated fatty acids with

the function of decreasing blood lipids and protecting

against cardiovascular disease, and their derivatives, have

been isolated from C. sinensis. The unsaturated fatty acid

content includes Cl6:1, Cl7:1, Cl8:l, and Cl8:2 (7).

Polar compounds of C. sinensis extracts include

many alcohols and aldehydes (1). Particularly interesting

is the range of polycyclic aromatic hydrocarbons produced

by many C. sinensis strains, named PAH compounds, for

which it was proposed to react with the polypropylene

used in common mushroom culture bags, resulting in the

production of byproducts toxic to C. sinensis and stunting

growth as time progresses (5). Of particular note are various

immunosuppressive compounds found in Cordyceps

spp., including cyclosporin from C. subsessilis (anamorph:

Tolypocladium inflatum) (14), and also compounds found

in Isaria sinclairii, a species closely related to the genus of

Cordyceps (3).

 

Preparation of Products

Various pure compounds, extracts, whole fungus, and

other preparations have been used in preclinical and clinical

studies, and several products are now available in the

market, mostly used as food supplements. In TCM, hotwater

extraction of whole fruiting bodies is traditionally

used. Nowadays, extracts of polysaccharides are mainly

obtained by hotwater extraction followed by ethanol precipitation

(15). For pure compounds, different types of

chromatography are used, mainly affinity, ion-exchange

or size-exclusion chromatography. It should be noted that

different types of extracts give different results in the studies

mentioned, but all of them show positive medicinal

value.

 

PRECLINICAL STUDIES

The widespread use of Cordyceps spp. in TCM has been

discussed above in the section on History and Traditional

Uses. One of the most significant proposed activities of

medicinal mushrooms is their role as immunomodulators.

Other activities ascribed to Cordyceps spp. are antitumor,

antimetastatic, immunomodulatory, anti-oxidant,

anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic,

hypoglycemic, anti-aging, neuroprotective and

renoprotective activities (2).

 

Cancer

A possibly valuable therapeutic application of Cordyceps

spp. is its potential as a treatment for cancer, and as an adjunct

to chemotherapy, radiation, and other conventional

and traditional cancer treatments (2,4). The mechanism

by which Cordyceps inhibits the growth of various cancer

cells might occur by one of several means: by enhancing

immunological function and nonspecific immunity; by selectively

inhibiting RNA synthesis, thereby affecting the

protein synthesis; by restricting the sprouting of blood

vessels (angiogenesis); by inducing tumor cell apoptosis;

by regulation of signal pathways; anti-oxidation and antifree

radical activity; anti-mutation effect; interfering with

the replication of tumor-inducing viruses; and by inducing

nucleic methylation (7).

Growth inhibition of various cancer cells by enhancing

immunological function and nonspecific immunity is

usually linked to polysaccharides, especially -D-glucans,

which present major cell wall structural components in

fungi and are also found in plants and some bacteria

but not in animals. Consequently, they are considered to

be classic pathogen-associated molecular patterns, called

as PAMPs (16). PAMPs potently trigger inflammatory responses

in a host, as if it was infected by a fungus. Studies

have shown that -D-glucans initiate biological response

with binding to complement receptor 3 (CR3) located

on the surface of the immune system effector cells, like

macrophages, thereby setting up different intercellular activities

of the immune system and leading to production

of cytokines, such as TNF-, interleukins, interferons, and

finally apoptosis of tumor cells (17). Toll-like receptors (especially

TLR-2) and dectin-1 receptor play an important

role in internalization and signaling responses to fungal

-D-glucans (18).

The anti-tumor effect also has been related to the

inhibition of DNA and RNA synthesis (19). Studies (20)

have demonstrated that cordycepin can selectively inhibit

mRNA synthesis, which affects protein synthesis by competing

with adenosine nucleoside phosphatase. The inhibition

may be blocked by adenosine. Cordycepin can also

kill leukemia cells and extend the period of mitotic cells

in the S and G phases. Nakamura et al. (21) found that,

with respect to cancer cells and normal cells, cordycepin

caused an inhibition rate of cell division on cancer cells of

55% while only 1.5% on normal cells.

Results show that cordycepin may have a very slight effect on the human body while treating cancer.

Another mechanism is inducing tumor cell apoptosis.

Extracts of C. militaris inhibited cell growth of human

leukemia cells in a dose-dependent manner (22), which

was associated with morphological change and apoptotic

cell death, such as formation of apoptotic bodies andDNA

fragmentation. Results indicated that the antiproliferative

effects were associated with the induction of apoptotic cell

death through regulation of several major growth regulatory

gene products (23).

In cancer research, there have been many studies

made with Cordyceps spp. extracts using animal models.

C. militaris inhibited the growth and metastasis of Lewis

lung cancer cells and the growth of sarcoma S180 cells

implanted in mice. In addition, the survival period of

the mice was increased (24). A study using murine models

verified that oral administration of a hot water extract

of C. sinensis consequently resulted in the activation

of macrophages, thereby increasing the production of

GM-CSF and IL-6, which act on the systemic immune

system (25). In another study (26), mice treated with

cyclophosphamide, which suppresses immune function,

and with C. sinensis hot water extract saw their immune

function return to normal, as measured by the IgM and

IgG response and macrophage activity.

 

Fatigue

Trials in the mouse swim test, conducted using C. sinensis

added to a standard diet compared with use of the untreated

standard diet, have invariably shown the use of

C. sinensis to significantly increase the time to exhaustion

in laboratory animals over their control groups (4). The use

of C. sinensis by athletes stems from publicity surrounding

the performance exhibited by the Chinese Women’s

Track and Field team at the Chinese National games in

1993. In this competition, nine world records were broken

by substantial margins. The team’s coach attributed

their success to C. sinensis (27). An increase in cellular ATP

level results in an increase in useful energy, in contrast

to the perceived increase in energy, which occurs from

the use of other stimulants, such as caffeine, ephedrine,

and amphetamines, ultimately resulting in an energy

deficiency (28).

Hypoglycemic Effects

In animal studies, isolated polysaccharides, have been

shown to improve blood glucose metabolism and increase

insulin sensitivity in normal animals, to lower blood sugar

levels in genetically diabetic animals, and to positively effect

blood sugar metabolism in animals with chemically

induced diabetes (29–31). The common thread throughout

all these trials is the increase in insulin sensitivity

and hepatic glucose-regulating enzymes, glucokinase and

hexokinase.

Lung Ailments

Mice treated with C. sinensis were able to survive up to

three times longer than those left untreated, demonstrating

a more efficient utilization of the available oxygen.

Such efficacy alludes to the use of C. sinensis as an effective

treatment for bronchitis, asthma, and chronic obstructive

pulmonary disease. A study was conducted using

in vivo mouse model-induced acute pulmonary edema,

which causes systemic lack of oxygen, acidic body, and

death. Research results show that animals taking C. sinensis

had a significantly greater survival rate of 20% mortality

in comparison with 80% mortality of the control

group (33).

Male & Female Sexual Dysfunction

C. sinensis has been used for centuries in TCM to treat

male and female sexual dysfunction, such as hypolibidinism

and impotence. Preclinical data on the effects of

C. sinensis on mice showed sex steroid–like effects (4), and

human clinical trials have demonstrated similarly the effectiveness

of C. sinensis in combating decreased sex drive

and virility (34). Treatment of rats on a diet supplemented

with C. militaris mycelium resulted in an increase of serum

cordycepin concentration, serum testosterone, and serum

estradiol-17 concentrations. They proposed that supplementation

with C. militaris improves sperm quality and

quantity in rats (35).

Cordyceps Antiviral Activity

The recognition of bacteria, viruses, fungi, and other microbes

is controlled by host immune cells with many innate

immunity receptors, such as Toll-like receptors, Ctype

lectin receptors, and immunoglobulin-like receptors.

Studies indicate that the immune modulating properties

of C. sinensis could be attributed to their polysaccharide

components. These polysaccharides specifically interact

with and activate surface receptors involved in innate immunity

(36). It was shown that intranasal administration

of an acidic polysaccharide, isolated from the extract of

C. militaris grown on germinated soybeans, decreased

virus titers in the bronchoalveolar lavage fluid and the

lungs of mice infected with influenza A virus. Furthermore,

it increased TNF-, IFN-, IL-1, IL-6 and IL-10 levels,

enhanced nitric oxide production, and induced iNOS

mRNA expressions in murine macrophage cells (37).

 

Cordycep CLINICAL STUDIES

Due to the historically high cost of the fungus and the

only recently developed methods for artificial cultivation,

clinical trials of C. sinensis and its extracts are still

relatively new endeavors. Earlier trials, although few in

number, have set the precedent from which modern trials

are building, expanding, and cementing our understanding

of Cordyceps spp. The majority of clinical trials

mentioned in this section used standard double-blind

placebo-controlled protocols. Approval was granted in the

countries where the trials were performed, but in most

cases the trials were conducted in China.

Cancer

The belief in the efficacy of C. sinensis against cancer is

widespread in the Orient, and many cancer patients in

Japan, Korea, and China are taking C. sinensis, or some

other mushroom-derived immunomodulators [such as

PSKTM, PSPTM, LentinanTM, AHCCTM, Immune AssistTM

(a heteropolysaccharide complex formula), and arabinoxylanes

(MGN3TM)], while undergoing conventional

treatment (1). Clinical studies involving cancer patients

have been conducted mostly in China and Japan (38,39).

In one study of 50 patients with lung cancer, who were

administered C. sinensis at 6 g/day, in conjunction with

chemotherapy, tumors were reduced in size in 46% of the

patients studied. A trial involving cancer patients with

several different types of tumors found that C. sinensis,

taken over a two-month period at 6 g/day, improved subjective

symptoms in the majority of patients. White blood

cell counts were kept at 3000/L, or higher; and even

with radiation or chemotherapy, other immunological

parameters showed no significant change, while tumor

size was significantly reduced, indicating an improved

tolerance for radiation and/or chemotherapy (1). In addition,

natural C. sinensis has been shown to enhance the

NK cell activity of normal patients by 74% and increased

the NK activity of leukemia patients by 400% (39).

Fatigue

In a placebo-controlled clinical study of elderly patients

with chronic fatigue, results indicated that most of the

participants treated with C. sinensis reported a significant

clinical improvement in the areas of fatigue, cold intolerance,

dizziness, frequent nocturia, tinnitus, hyposexuality,

and amnesia, while no improvement was reported in the

placebo group (4,40–42). Another study involving healthy

elderly volunteers, with an average age of 65, tested the

output performance and oxygen capacity of participants

while exercising on stationary bicycles. A portion of the

volunteers consumed C. sinensis for six weeks, while others

consumed a placebo. The results demonstrated that

the C. sinensis group had a significant increase in energy

output and oxygen capacity over the placebo group after

six weeks of the study (43). The presence of adenosine,

cordycepin, D-mannitol, polysaccharides, vitamins, and

trace elements may be, at least partially, the cause for such

effects.

Kidney Ailments

Traditional views of the Cordyceps spp. held that its consumption

strengthened the kidneys. In a study of 51 patients

suffering from chronic renal failure, it was found

that C. sinensis significantly improved both the kidney

function and overall immune function of treated patients,

compared with the untreated control group (44). Patients

with chronic renal failure or reduced kidney function often

suffer from hypertension, proteinuria, and anemia. After

a one-month treatment with C. sinensis, patients showed

a 15% reduction in blood pressure, reduction in urinary

protein, and increases in superoxide dismutase (44). Fiftyone

percent improvement of chronic kidney diseases was

shown only one month after taking C. sinensis supplement

(45). In another clinical study, treatment with C. sinensis

of patients having gentamicin-induced kidney damage resulted

in the recovery of 89% of their normal kidney function

after six days, compared with only 45% recovery by

patients treated with more conventional methods (1).

Hypoglycemic Effects

In a randomized trial, 95% of patients treated with C. sinensis

showed improvement in their blood sugar profiles,

while the control group showed only 54% improvement

with treatment by other methods (46).

Cordyceps Lung Ailments

There have been many trials in humans, using Cordyceps

spp. to treat many respiratory illnesses, including asthma

and bronchitis, either alone or as an adjunct to standard

antibiotic therapy, and it appears to be useful for all of

these conditions (47–50). Extracts of C. sinensis have been

shown to inhibit tracheal contractions, especially important

in asthma patients, since it allows for increased airflow

to the lungs. In addition, its anti-inflammatory properties

may prove to bring further relief to asthma patients,

whose airways become obstructed, due to an allergic reaction

resulting in the swelling of the bronchial pathways

(1). In a double-blind placebo-controlled study with 30

elderly volunteers, C. sinensis significantly improved the

maximum amount of oxygen these people were able to

assimilate (51).

Heart Ailments

It has been shown that C. sinensis, which often has a significant

quantity of adenosine, along with adenosine-type

nucleotides and nucleosides, has an effect on coronary and

cerebral circulation (52,53). In studies of patients suffering

from chronic heart failure, the long-term administration of

C. sinensis, in conjunction with conventional treatments,

promoted an increase in the overall quality of life (42). This

included general physical condition, mental health, sexual

drive, and cardiac function, compared with the control

group. Studies have also shown the benefits of C. sinensis

on heart rhythm disturbances, such as cardiac arrhythmias

and chronic heart failure (54).

Liver Ailments

In the Orient today, C. sinensis is commonly used as an

adjunct in the treatment of chronic hepatitis B and C. In

one study, C. sinensis extract was used in combination with

several other medicinal mushroom extracts as an adjunct

to lamivudine, for the treatment of hepatitis B. The group

receiving C. sinensis along with other medicinal mushroom

extracts had much better results in a shorter period

of time than the control group, who received only

lamivudine (55). Treatment of 22 patients, diagnosed with

posthepatic cirrhosis, with C. sinensis (56), showed improvement

in liver function tests, and in another trial on

patients with hepatitis B and patients with cirrhosis taking

C. sinensis supplement showed around 80% improvement

of liver functions (57).

Hypercholesterolemia

In both human and animal studies, administration of

C. sinensis has been associated with cholesterol and triglyceride

reduction and an increase in the ratio of HDL to

LDL cholesterol (1). As such it may prevent, arrest, and

even reverse coronary atherosclerosis (58). The studies

have demonstrated that C. sinensis helps to lower total

cholesterol up to 21% and triglycerides up to 26%.

At the same time it helps to increase HDL cholesterol

up to 30% (54).

Antiviral Activity

After three months of treatment of chronic hepatitis B

patients using C. sinensis, CD4 and CD4/CD8 ratios increased

significantly (59). The results suggest that beneficial

effects might be obtained through adjustment of the T

lymphocyte subsets level. Treatment of 65 cases (with 20

cases in the control group) of patients with posthepatic cirrhosis

has shown similar results (60). Extracts of Cordyceps

spp. are also effective against HIV infections. A C. sinensis

containing formula named Immune Assist 24/7TM has recently

been introduced throughout West Africa for use in

treating HIV infections and other immune-deficient states

(2), and is quite popular with both the doctors and the

patients due to its low toxicity and cost when compared

with other antiretroviral drug options.

Dosage

Because clinical data on Cordyceps spp. is relatively new,

and even more so in Western Countries, recommended

dosage requirements may vary, depending on the source.

In general, clinical trials have been conducted using 3 to

4.5 g of C. sinensis per day, except in cases of severe liver

disease, where the dosage has usually been higher, in the

range of 6 to 9 g per day (4). There are some practitioners

known to these authors, who keep their cancer patients

on 30 to 50 g of C. sinensis per day. While this may seem

excessive, the clinical results seen with this treatment regimen

are promising, and Cordyceps spp. related toxicity has

never been reported.

C. sinensis has been traditionally taken in tea or eaten

whole, either by itself or cooked with a variety of meats.

Today, in addition to the established traditional means of

consumption, powdered mycelium and mycelial extracts

are also available in capsulated and noncapsulated form.

At present, there are no reliable standards by which to

compare different brands, but in general, the quality of

Cordyceps spp. is improving, as methods of more efficient

cultivation are investigated; and as more clinical trials are

conducted, a clearer picture of recommended dosages for a

particular condition will become more standardized. Considering

the quality of cultivated Cordyceps spp. available

in the market today and the risk of lead exposure as well

as the cost, such as with wild C. sinensis, the use of natural

Cordyceps spp., over the artificially cultivated variety, is

not recommended. Obtaining Cordyceps spp. from a reliable

source, with complete analytical data provided, is the

safest way to purchase species of Cordyceps.

Safety Profile

None known contraindications.

Drug Interactions

There is observational evidence that the alteration of the

body’s blood glucose metabolism in patients consuming

Cordyceps spp. often results in the reduction of oral or

injected anti-diabetic medications. It is also posited that

the naturally occurring antiretroviral compounds found

in C. sinensis (e.g., 2,3-dideoxyadenosine) are marketed as

a major anti-HIV drug under the name Videx and Didanosine,

as well as 3-deoxyadenosine (which has the

same or at least similar activity); C. sinensis could result

in increased effectiveness or decreased dosage requirements

for patients undergoing concurrent therapy with

other antiretroviral drugs. Caution should be exercised

in these patients, especially considering the newer, more

potent hybrid strains of Cordyceps spp. being developed,

and the targeted medicinal compounds being selectively

cultivated.

Adverse Side Effects

Very few toxic side effects have been demonstrated with

Cordyceps spp. use, although a very small number of people

may experience dry mouth, nausea, or diarrhea (1).

One study reported that a patient had developed a systemic

allergic reaction after taking a strain of cultivated

C. sinensis called Cs-4 (61); however, this type of reaction

is not common. There is little published data on the use

of Cordyceps spp. in pregnant or lactating women, or in

very young children, and appropriate precautions should

be taken with these types of patients.

 

Toxicity

No human toxicity has been reported, and animal models

failed to find an LD50 (median lethal dose) injected IP in

mice at up to 80 g/kg per day, with no fatalities after seven

days (2). Given by mouth to rabbits for three months, at

10 g/kg per day (n = 6), no abnormalities were seen from

blood tests or in kidney or liver function (62).

REGULATORY STATUS

Cordyceps spp. remains, in many nations throughout

the world, an unrecognized substance. Other than import/

export taxes and restrictions, which vary from country

to country (many of which ban the import of any

such substance), most governments do not require a prescription

to purchase or use Cordyceps spp. Among the

few countries that do require a doctor’s prescription are

Portugal, Romania, and Austria. Many governments require

that vendors obtain a special license to distribute

any product relating to human health.

In the United States, Cordyceps spp. are marketed

privately and considered by the FDA as a dietary supplement.

GRASapplications referring to Cordyceps spp. status

as a food additive are unavailable; however, a premarket

notification to the FDA regarding species of Cordyceps,

containing in-depth information relating to preclinical trials

and toxicology studies, has been available to the public,

via the FDA website.

CONCLUSION

When a natural product, such as C. sinensis, has such a

long history of use, it seems logical that there is quite likely

some truth behind the myths. Our challenge in the modern

age is to scientifically unravel the many claims and

conflicts. With C. sinensis this challenge has been greater

than with many other herbals due to the enormous cost

and scarcity of the material. We are fortunate that we

live in an age of such rapidly expanding biotechnological

progress. For now, we have ways at our disposal to

produce Cordyceps spp. in large enough volume, and at a

low enough cost, that research becomes possible to nearly

anyone interested in looking at this unique organism.