Summer-mushroom, Winter-worm: History and Tradition

Himalayan plateau, Tibet.
(Source: theancientweb.com)

Cordyceps fungus is a rare and highly valued herb in Traditional Chinese Medicine (TCM), its medicinal uses taking root around 2000 years ago. There are over 600 species in the genus, with Cordyceps sinensis (Cs or "DongChongXiaCao”) bearing a special significance.  Wild Cs is only found high in the Himalayan Plateau and develops in a remarkable manner (Halpern, 2007). It is a parasite, infecting an underground-dwelling caterpillar in late fall and completely consuming it by early summer. Feeding on the caterpillar’s nutrients, the mushroom grows and is harvested as soon as it protrudes from the ground (Halpern, 2007).

 

C.sinensis in natural habitat, Tibet.
(Holliday & Cleaver, 2008)

The first scientific record of Cordyceps sinensis as a medicinal herb dates back to 1757 AD China in an encyclopedia titled: New Compilation of Materia Medica (Ben-Cao-Cong-Xin) (Zhu, Halpern, Jones 1998). These records prescribe Cordyceps sinensis for treatment, protection, and enhanced function of lung and kidneys as well as “Yin Yang double invigoration” (Zhu et al, 1998). In addition to these early uses, Cs was administered as a prophylactic agent to prolong life, treat impotence, liver diseases, and arrhythmias as well as to improve memory (Halpern, 2007). Being such a rare herb it was only used by cultures of Tibet, Mongolia, and the Chinese elite (Zhu et al, 1998).

The array of traditional methods to administer Cordyceps corresponds to the enormous collection of it purposes. The simplest and earliest way of consumption was eating whole, raw mushroom, equivalent to approximately 8 or 9 grams (Halpern, 2007; Holliday & Cleaver, 2008). Another common approach is preparing a tonic by cooking Cs mushrooms in water or consuming a dried powder (Zhu et al., 1998). There are, specific ways to prepare the mushroom depending on the type of illness targeted (Table 1). The Mykot tribe, originating from Tibet, traditionally prepares a yogurt from skim yak milk and harvested Cs mushrooms (Halpern, 2007). While cancer patients in China were prescribed to cook the whole mushroom (with the caterpillar body attached) inside the stomach of a duck. The mushroom was then removed and the duck would be eaten for 8 to 10 days or until healthy (Halpern, 2007).

Table 1: Traditional combinations of C.sinensis with foods to target
specific conditions. (Adapted from Zhu et al., 1998)

Active Components: Small Molecules That Do Big Things

Cordyceps contains a large number of biologically active and beneficial molecules, which reflects the wide array of its applications. Pharmacologically active compounds have not yet been fully resolved, however cordycepin, cordycepic acid, ergosterol  and cordyceps polysaccharide are the major proposed candidates (Cleaver, Holliday & Wasser, 2005). Cordycepin specifically has been deemed effective in suppressing inflammation as well as tumor invasion, migration, and growth (Zhou et al., 2009). Ergosterol and cordyceps polysaccharide are other bioactive constituents with both immune-enhancing and tumor-suppressing qualities (Cleaver et al., 2005).

Major active components of C.sinensis.

Other physiologically beneficial constituents include a compilation of vitamins (B1, B2, B12, E, and K), as well as some important metals (calcium, magnesium, sodium, potassium, iron, zinc, etc.) (Zhu et al., 1998).  Much of the prophylactic benefits of C.sinensis could be attributed to the molecules mentioned above in addition to significant concentrations of all essential amino acids, saturated and unsaturated fatty acids, as well as other peptides, proteins and polysaccharides (Cleaver et al., 2005). While certain components have been isolated and examined for their activity, it is also possible that all or some of these constituents act synergistically (Zhu et al., 1998).

The most common method of administration of Cordyceps is an aqueous extract, or tonic, which is also the form used in all scientific studies. To prepare the tonic, Cordyceps is finely ground and boiled in distilled water for about 1 hour (Li, Yang & Tsim, 2006). The proportions are standardized at 7 grams of powder per 100 milliliters of water, although these numbers may vary (Li et al., 2006). Capsules containing dry, ground fungus are also readily available.

Cordyceps in Modern Medicine: What the Science Says.

Cordyceps is one of the most intensively researched TCM herbs largely due to its cancer-fighting properties. However, it would be fair to say that its primary use is as an immune boosting agent (Koh, et al., 2002). Although mechanisms of action of Cordyceps in cancer remain to be devised, a progressively increasing body of work suggests that most of the tumor-suppressive effect is achieved through activation of the immune system or by induction of apoptosis (Yu et al. 2004; Jordan, Nowak, Lee 2009) . Well-documented clinical trials, however, are lacking and most studies to date were performed using cancer cell lines or mouse models (Zhou et al., 2009).

Conquering Cancer

Macrophages attack cancer cells.
Source: axisorigin.com

In a recent study, S.E. Park and colleagues (2009) looked at the effect of aqueous Cordyceps extract in immune deficient mice xenografted with human lung cancer cells. Use of nude mice with human cell lines is a common method to measure anti-tumor action of a therapeutic agent (Park et al., 2009). The investigation was based on previous in vitro studies looking at tumor growth inhibition by administration of hot water extract of Cs (Sung et al., 2002; Kim et al., 2001). It was generally found that mice treated with 300 mg of Cordyceps per kilogram body weight per day showed significant reduction in tumor mass and volume. The mice in this experimental group also survived approximately 4-7 days longer, however these results were not statistically significant due to error.

Source: nature.com

The suitability of experimental set up is supported by the fact that there was a significant reduction of tumor volume in the mouse models compared to the control. However, the method is not effective in measuring effects on survival rate, amelioration of symptoms or effectiveness in conjunction with chemotherapy, which would be a requirement for human subjects. Such experiments establish the ground for clinical use of a given drug, but are largely inconclusive as to how the agent will act in a human setting. The experiment does not reflect the etiology nor body chemistry in a human cavity. Despite the drawbacks, the results of this and other numerous in vivo and in vitro studies demonstrate, Cordyceps extract is effective in tumor regression assays when applied to human cancer cells.

Boosting the Immune System

Macrophage attacks a fungal spore.
Source: dv.com

With respect to its immune-boosting action, a study was conducted by Jordan and colleagues (2008), which demonstrated that aqueous C. sinensis extract activated murine macrophages in vitro. Administration of Cs caused macrophages to release cytokines as well as nitric oxide, which are both markers of macrophage activation and are the molecules used to target bacterial infections. The experiment has also shown to significantly decrease the bacterial load in vivo (in murine models) and speed up recovery from a Listeria monocytogenes infection based on a statistical analysis. Resolution of this infection directly depends on the level of activation on macrophages, thus further demonstrating that C. sinensis is capable of enhancing and modulating innate immunity.

Macrophage engulfing Streptococcus
bacteria.
Source: allstarhealth.com

The methods chosen by Jordan allow for logical set up and progression of the experiment, primarily demonstrating that Cs does in fact activate macrophages in a dose-dependent manner. This led to the in vivo experiment, which has shown reduced bacterial load, due to increased macrophage recruitment. Since the experiment was performed in vivo it was not determined exactly whether the reduced bacterial load was due solely to increased number of activated macrophages or whether other immune system cells had a role to play.

Although much remains to be done, the existing body of research points to immense therapeutic benefits of the Cordyceps fungi for both cancer and the immune system (Holliday & Cleaver 2005). With respect to evidence based medicine, its application and effectiveness in humans in conjunction with western medicine practices should be investigated further, yet the 2000-year old history of use should not be overlooked.

Up-regulation of macrophage recruitment by Cordyceps, allows for efficient
attack of cancer cells and pathogens, as well as prevention of metastasis.

Need to Know: Cautions, Side-effects and Interactions

Cordyceps is deemed a very safe herb, with no known contraindications or toxicity (Holliday & Cleaver 2008). Studies in a variety of animal models have shown that a lethal dose could not be detected, nor has any type of mutagenic or harmful effects on bodily functions been discovered (Cleaver et al., 2005). Few side effects have been reported and are limited to nausea and stomach uneasiness, accompanied in some cases by dry mouth (Zhou et al., 1998). Only a single report of a systemic allergic reaction to cordyceps exists (Zhou et al., 1998).

Cordyceps is frequently used in medicinal mushroom mixtures working synergistically to fight cancer, reduce inflammation and alleviate toxicity in anti-retroviral therapy (Holliday & Cleaver, 2008; Smith, Rowen & Sullivan, 2005; Wang et al., 2001). Drug interactions are few, especially with antiretroviral and insulin medication among others, leading to a lesser amount of the drug to be used (Holliday & Cleaver 2008). 

Cordyceps and other medicinal mushrooms described by
Dr. Georges Halpern in his book "Healing Mushrooms".

Due to the known effect of cordyceps to enhance glucose metabolism and insulin sensitivity, it is known to decrease the amount of insulin injections required by diabetic patients (Guo, Han & Lio, 2010; Zhu et al. 1998). In vitro studies have shown inhibition of human platelet aggregation, which suggests that high doses of cordyceps may potentiate anticoagulants (Cho et al., 2007). The adenosine component of cordyceps is also marketed as an anti-HIV drug. Anti-retroviral drugs are toxic, thus caution should be taken when using these therapies in conjunction with high doses of cordyceps (Holliday & Cleaver, 2008).

Currently, more potent types of Cordyceps are being cultivated, thus there is always potential for drug interactions especially when high doses are consumed (Cleaver et al., 2005).

Sources

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Guo, J.Y., Han, C.C., Liu, Y.M. A Contemporary Treatment Approach to Both Diabetes and Depression by Cordyceps sinensis, Rich in Vanadium. eCAM 7(3):  387-389 (2010).

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