Study type: 

Systematic review

Purpose:

To explore the anti-neuroinflammatory (the ability to reduce or counteract neuroinflammation, which is the inflammation of neural tissue in the brain or nervous system, often associated with various neurological disorders) activities of medicinal mushrooms, including Cordyceps in various laboratory studies and animal studies. 

Results:

Cordyceps militaris is known for its bioactive compound, cordycepin.  Numerous studies have highlighted cordycepin's positive effects, especially in the central nervous system (which consists of the brain and spinal cord), where it demonstrates anti-neuroinflammatory properties, meaning that they have properties that counteract inflammation in the brain and nervous system. 

One rodent study revealed that cordycepin from Cordyceps militaris offers advantages against chronic unpredictable mild stress in mice with behavioural deficits. Other research found that it reduced depressive-like behaviours and decreased inflammation in mice. Further studies suggest that cordycepin, along with a hot water extract from Cordyceps militaris, has exhibited the ability to shield brain cells during reduced blood flow, reducing damage from harmful molecules and lowered the activation of certain brain cells, indicating neuroprotective effects.

One study on rodents demonstrated that cordycepin, derived from Cordyceps militaris, countered the effects of chronic unpredictable mild stress, improving the behaviour of the mice. It has also been found that cordycepin reduced depressive-like behaviours and decreased inflammation in mice. 

Further studies found that cordycepin, in combination with a hot water extract from Cordyceps militaris, protected brain cells during periods of reduced blood flow, reducing damage from harmful molecules, indicating neuroprotective effects.

Year:

2020

Link:

https://doi.org/10.1016/j.tifs.2020.07.029

Study type: 

Rodent study

Purpose:

To assess the anti-ageing effects of Cordyceps sinensis in aged and castrated mice. 

Method of evaluation:

Learning and memory were assessed using water maze and step-down type avoidance tests. The water maze test measures spatial learning and memory in animals by requiring them to find a hidden platform in a pool of water using visual cues. The step-down type avoidance test evaluates learning and memory in rodents by measuring their ability to associate an elevated platform with a foot shock and subsequently avoid stepping down.

Sexual activity of male mice was estimated by copulation behaviour after a female rat in estrus (a specific stage in the reproductive cycle when mating and conception are most likely to occur) was placed into the male’s cage. 

Penis erection was evaluated using a laboratory apparatus in which an electrode was placed on the penis of male mice, and continuous electric shocks were administered until the penis achieved an erection. The time taken from the shock application to the onset of erection was measured as the penis erection latency.

Dose:

1.0, 2.0, or 4.0 g/kg of Crodyceps sinensis extract or controls

Duration:

6 weeks

Results:

The study found that doses of 2.0 and 4.0 mg/kg of cordyceps sinensis extract significantly improved learning and memory in aged mice compared to normal controls, in both water maze test and step-down  avoidance tests. Among mice treated with the highest dose (4.0 g/kg) of Cordyceps, the cellular structure in the hippocampus (a region within the brain responsible for memory and learning) remained well-preserved, with no signs of swelling. This observation suggests that cordyceps sinensis extract has a protective effect on the cellular structure of the hippocampus in aged mice, potentially contributing to its anti-ageing effect.

The study also found that cordyceps sinensis shortened penis erection latency (the time it takes for the penis to become erect in response to a stimulus) and mount latency (the time it takes for a male animal to mount a female for sexual activity) in castrated mice, indicating a positive impact on sexual function.

In addition, cordyceps sinensis extract improved the activity of antioxidative enzymes in aged mice, indicating its antioxidative effect. The study further discovered that the extract lowered the activity of monoamine oxidase (an enzyme that breaks down neurotransmitters in the brain) in aged mice, suggesting potential for enhanced brain function and prevention of age-related cognitive decline.

Overall, these findings suggest that cordyceps sinensis extract has a potential anti-ageing effect by improving brain function, antioxidative enzyme activity, and sexual function.

Year:

2011

Link:

https://doi.org/10.1002/ptr.2576

Study type: 

Rodent study

Purpose:

To investigate the lifespan-extending effect of Cordyceps sinensis in normal mice.

Dose:

500, 1000, and 1500 mg/kg body weight of Cordyceps sinensis or control

Results:

All the control mice died before reaching 3 years of age, while the mice receiving Cordyceps sinensis had an extended lifespan. The extension in lifespan varied depending on the dose of Cordyceps sinensis, with an increase of 10-66 days when half of the mice survived (50% survival) and 45-153 days when only 10% of them survived. 

The age of the oldest surviving mice was extended by 154 and 258 days at 500 mg/kg and 1500 mg/kg doses, respectively, after Cordyceps sinensis treatment. The highest effect was observed at a dose of 1000 mg/kg, which was extended by 354 days.  

Year:

2011

Link:

https://doi.org/10.1096/fasebj.25.1_supplement.599.1

Study type: 

Fruit fly study

Purpose:

To investigate the effects of Cordyceps sinensis on the lifespan of fruit flies. 

Dose:

0.02, 0.06, 0.20 mg/ml of Cordyceps sinensis oral liquid or control

Duration:

55 days

Results:

The results showed that lifelong treatment with Cordyceps sinensis significantly prolonged the lifespan of fruit flies.  Fruit flies typically live 40-50 days, but the average lifespan of the fruit flies was extended by 44, 46 and 47 days with Cordyceps sinensis at doses of 0.02, 0.06, 0.20 mg/ml, respectively. The maximum lifespan (the average lifespan of the longest surviving 10% of fruit flies) was extended by 67-69 days with the highest effect observed at the 0.06 mg/ml dose (69 days). 

Year:

2015

Link:

https://doi.org/10.3892/ijmm.2015.2296

Study type: 

Randomised, double-blinded, placebo-controlled clinical trial

Purpose:

To determine the effects of Cordyceps militaris on high intensity exercise in healthy  adults

Dose:

4 g/day of mushroom blend containing Cordyceps militaris (3 x 1.3 g capsules) or placebo (4 g of maltodextrin)

Participants:

28 recreationally active adults aged 18-35 years for Phase 1 (week 1); 10 volunteered to complete phase II (additional 2 weeks).

Duration:

1-3 weeks 

Results:

The study revealed that one week of supplementation with Cordyceps militaris did not lead to significant improvements in performance compared to the placebo. However, during a three-week period of taking the supplements, the researchers noticed that the participants' maximal oxygen consumption improved. This means that their aerobic capacity, or their body's ability to perform endurance activities, improved. 

There were also indications of potential improvements in the ventilatory threshold and time to exhaustion, indicating improved endurance and the ability to sustain higher exercise intensities for a longer duration. These findings suggest that longer-term or chronic supplementation with Cordyceps militaris may benefit exercise performance.

Year:

2016

Link:

https://doi.org/10.1080/19390211.2016.1203386

Study type: 

Double-blinded, placebo-controlled, prospective clinical trial

Purpose:

To examine the effect of cordyceps sinensis on exercise performance in healthy elderly subjects.

Dose:

999 mg/day of cordyceps sinensis (3 x 333 mg capsules) or placebo

Participants:

20 males and females, aged 50-75 years

Duration:

12 weeks 

Results:

After 12 weeks of cordyceps sinensis supplementation, there was a significant 10.5% increase in the metabolic threshold and an 8.5% increase in the ventilatory threshold. The metabolic threshold represents the point during exercise when the body starts using more anaerobic energy due to insufficient oxygen supply, leading to fatigue. The ventilatory threshold represents the point when the breathing rate increases to meet the increased oxygen demands of the muscles, allowing for better endurance during exercise. These improvements in both thresholds indicate an enhanced ability to sustain higher levels of exercise intensity.

These improvements were not observed in the placebo group, suggesting that cordyceps sinensis supplementation specifically contributed to the enhanced thresholds. On the other hand, no notable changes were observed in the maximum oxygen uptake, maximum heart rate, maximum work rate, or maximum ventilation in either group when compared to baseline. 

Year:

2010

Link:

https://doi.org/10.1089/acm.2009.0226

Study type: 

Rodent study

Purpose:

To evaluate the effect of Cordyceps sinensis supplementation on exercise endurance of rats.

Dose:

200 mg/kg body weight of Cordyceps sinensis mycelia powder or control

Additional intervention:

The exercise groups were subjected to swimming training for 15 days (6 days a week)

Duration:

15 days

Results:

Cordyceps sinensis treatment with and without exercise significantly improved swimming endurance in rats, by 2.9-fold in rats who exercised and 1.79-fold in rats who did not exercise, compared to placebo rats. Additionally, the study found that treatment with Cordyceps sinensis resulted in increased expression of skeletal muscle metabolic regulators. These regulators are proteins and enzymes that help regulate important metabolic processes within muscle cells, indicating an enhancement in the metabolic activity of the muscles. These findings suggest that Cordyceps sinensis supplementation can improve muscle performance and metabolic regulation, even without exercise, providing molecular evidence of its beneficial effects.

Year:

2011

Link:

https://doi.org/10.1016/j.jep.2011.04.040

Study type: 

Rodent study

Purpose:

To investigate the effect Cordyceps militaris polysaccharide on physical fatigue induced in mice through a forced swimming test.

Method of evaluation:

The mice in all groups underwent the forced swimming test 30 minutes after the final administration of Cordyceps militaris. The mice were considered fatigued when they were unable to reach the water surface to breathe within a 7-second period, which served as an indicator of swimming capacity.

Dose:

40, 80, 160 mg/kg body weight/day of Cordyceps militaris polysaccharide or control (drinking water)

Duration:

28 days

Results:

The study found that Cordyceps militaris polysaccharide has anti-fatigue properties and can lower serum urea nitrogen (UN) levels. During intense exercise, the body breaks down proteins and amino acids to produce energy, which increases UN levels. However, the study found that Cordyceps militaris polysaccharide can reduce the breakdown of proteins, leading to lower UN levels. This suggests that Cordyceps militaris polysaccharide may delay physical fatigue by preserving proteins and slowing down the onset of exhaustion.

Additionally, Mice treated with Cordyceps militaris polysaccharide at doses of 40, 80, and 160 mg/kg body weight exhibited significantly longer exhaustive swimming times, with increases of 29.81%, 45.22%, and 70.39% respectively compared to the control group.

These findings indicate that Cordyceps militaris polysaccharide holds potential as a new functional food or medicine for combating fatigue.

Year:

2016

Link:

https://doi.org/10.1615/IntJMedMushrooms.v18.i12.30

Study type: 

Rodent study

Purpose:

To investigate the effects of cordycepin (a principal active ingredient from Cordyceps militaris) on physical fatigue in mice.

Dose:

20 and 40 mg/kg of cordycepin or  500 mg/kg of taurine (a commonly used dietary supplement to relieve fatigue) or control (saltwater)

Duration:

28 days

Results:

The study found that both the 20 mg/kg and 40 mg/kg doses of cordycepin significantly increased the swimming time of weight-loaded mice. Taurine also exhibited a positive effect. Furthermore, cordycepin was found to reduce levels of lactic acid, which is associated with fatigue and muscle soreness following intense physical activity. Moreover, cordycepin increased the levels of energy metabolites (compounds involved in energy production) and antioxidants such as superoxide dismutase, glutathione, and NADP+. These findings suggest that cordycepin may alleviate fatigue by enhancing energy production, regulating energy metabolism, and increasing antioxidants.

Year:

2022

Link:

https://doi.org/10.1016/j.bbrc.2022.11.010

Study type: 

Rodent study

Purpose:

To investigate the anti-fatigue and anti-stress effects of Cordyceps sinensis mycelia in mice. 

Dose:

150 and 300 mg/kg/day Cordyceps sinensis via a stomach tube

Results:

The swimming endurance of mice improved significantly when they were administered with Cordyceps sinensis mycelia at doses of 150 and 300 mg/kg per day. This resulted in a prolonged swimming time from 75 to 90 minutes and reduced fatigue. It effectively suppressed weight changes in the adrenal gland, spleen, thymus, and thyroid, potentially indicating a mitigating effect on stress-induced changes in these tissues. Furthermore, the hot water fraction inhibited an increase in total cholesterol and a decrease in alkaline phosphatase, which are biochemical indicators of the stress that arises when individuals are unable to move or change positions freely, resulting in feelings of discomfort, tension, and occasionally anxiety or frustration (known as immobilisation stress).

Year:

2003

Link:

https://doi.org/10.1248/bpb.26.691

Study type: 

Rodent study

Purpose:

To evaluate the anti-fatigue effects of Cordyceps militaris on mice. 

Dose:

First group: 5, 10, and 20 g/kg of Cordyceps militaris combined with extruded products of cereal grains. Extruded products of cereal grains are food items made by processing cereal grains, like wheat or corn, through a machine that applies heat and pressure.

Second group: 5, 10, and 20 g/kg of the extruded product of cereal grains alone.
Third group: control (distilled water)

Duration: 

30 days

Results:

Both the extruded product of cereal grains alone and in combination with Cordyceps militaris were able to prevent exercise-induced fatigue in mice. However, the extruded product of cereal grains with Cordyceps militaris were superior in relieving fatigue compared to the extruded product of cereal grains alone. 

The study showed that supplementing mice with Cordyceps militaris reduced fatigue, improved their endurance during exercise, lowered muscle damage and stress, and decreased oxidative stress. Oxidative stress happens when there are too many harmful molecules called free radicals in the body, which can contribute to fatigue. Cordyceps helps by reducing these free radicals, protecting the cells from damage, and leading to higher energy levels and less fatigue.

Year:

2017

Link:

https://doi.org/10.1186/s12970-017-0171-1

Study type: 

Randomised clinical trial

Purpose:

To investigate whether Cordyceps sinensis can regulate the immune system in kidney transplant patients. 

Dose:

3.0 g/day of Cordyceps sinensis (3 x 1.0 g capsule)

Participants:

182 transplant recipients with an average age of 38 years

Duration:

12 months

Results:

The group treated with Cordyceps sinensis reported having fewer complications after the transplant compared to the group that didn't take Cordyceps. Additionally, the group treated with Cordyceps exhibited higher levels of IL-10, a substance known for its anti-inflammatory properties. No serious side effects were observed.

Year:

2011

Link:

https://doi.org/10.2741/e245

Study type: 

Rodent study

Purpose:

To evaluate the effect of Cordyceps cicadae extract in mice with testicular damage.

Dose:

50, 100, and 400 mg/kg body weight/day of Cordyceps cicadae extract rich in nucleosides 

Duration:

7 days 

Results:

Cordyceps treatment significantly restored testes weight loss, improved the testes index, and enhanced sperm parameters such as counts, viability, and motility in mice with testicular damage. Additionally, cordyceps treatment resulted in a significant increase in levels of testosterone and follicle-stimulating hormone. Elevated levels of serum testosterone indicate improved male hormonal balance, potentially leading to enhanced sexual function, while increased levels of follicle-stimulating hormone indicate that the reproductive organs are being properly stimulated, which is important for healthy reproductive function. Cordyceps also restored antioxidant activities in the testes and reduced inflammation. Improved antioxidant activity and reduced inflammation may protect the testes from damage and support the optimal functioning of sperm cells. Overall, these findings indicate that the treatment holds promise for improving male reproductive health.

Year:

2020

Link:

https://doi.org/10.1002/cbdv.202000671

Study type: 

Rodent study

Purpose:

To explore the effects of cordycepin, a compound found in Cordyceps militaris, on testicular function in middle-aged rats.

Dose:

5, 10, 20 mg/kg of cordycepin or control

Duration:

4 months

Results:

Cordycepin improved sperm motility or movement, which is essential for successful fertilisation as sperm needs to reach and penetrate the egg. Specifically, a dosage of 20 mg/kg body weight was particularly effective in enhancing testicular function in middle-aged rats. Cordycepin administration also led to a slight increase in testosterone levels in middle-aged rats; however, this increase was not statistically significant. The findings suggest that cordycepin has the potential to restore normal testicular function and may serve as an effective pharmacologic agent to counteract the decline in testicular function associated with ageing.

Year:

2012

Link:

https://doi.org/10.1055/s-0032-1315212

Study type: 

Rodent study

Purpose:

To investigate the protective effects of Cordyceps militaris extract in mice with reproductive damage induced by bisphenol A (BPA),  a compound that can harm the testicles causing oxidative stress. Oxidative stress occurs when there are too many unstable molecules called free radicals in the body and not enough antioxidants to get rid of them, causing damage to organs and tissues.

Dose:

200, 400, 800 mg/kg body weight/day of Cordyceps militaris extract

Duration:

28 days 

Results:

Cordyceps militaris protected against reproductive damage caused by BPA (bisphenol A). Mice exposed to 200 mg/kg BPA for 4 weeks experienced reproductive damage, but treatment with Cordyceps militaris reduced this damage. Cordyceps militaris significantly increased the levels of natural antioxidants in the testicles and reduced markers of oxidative stress. 

Furthermore, Cordyceps militaris treatment significantly increased luteinizing hormone and testosterone levels in the blood, which can improve sperm count and motility. These findings demonstrate the potential of Cordyceps militaris as a natural substance to prevent reproductive damage caused by BPA.

Year:

2012

Link:

https://doi.org/10.1080/19396368.2016.1182234

Study type: 

Cellular study (in-vitro)

Purpose:

To investigate the effects of Cordyceps sinensis on testosterone production in Leydig cells from male mice. Leydig cells are specialised cells found in the testes and are responsible for the synthesis and release of testosterone.

Dose:

3 mg/ml of Cordyceps sinensis

Results:

The study showed that Cordyceps sinensis at a concentration of 3 mg/mLl significantly increased the production of testosterone in Leydig cells. The researchers also investigated when the stimulation of testosterone production by Cordyceps sinensis was at its peak and found that it occurred between 2 to 3 hours after administration.

Year:

2001

Link:

https://doi.org/10.1016/s0024-3205(01)01339-x

Study type: 

Rodent study

Purpose:

To investigate the effects of Cordyceps militaris on sexual performance and erectile function in diabetic male rats. It is important to note that diabetes is strongly associated with sexual dysfunction in males.

Dose:

0.1, 0.5, and 1.0 g/kg/day of Cordyceps militaris or a single administration of 5 mg/kg of sildenafil (Viagra), or control

Duration:

3 weeks

Results:

The study revealed that daily administration of Cordyceps militaris at doses of 0.1 and 0.5 g/kg, as well as a single administration of Viagra, resulted in a significant increase in sperm count, sperm motility, testosterone levels, and overall improvement in sexual function. Additionally, the levels of penile nitric oxide synthase (NOS) and testicular superoxide dismutase (SOD) activities were significantly increased. Higher levels of penile nitric oxide synthase can promote better blood flow and enhance erectile function, while increased testicular superoxide dismutase activity can potentially preserve testicular health and function.

However, the 1 g/kg Cordyceps militaris treatment did not demonstrate statistical significance in the previously mentioned parameters, except for its effect on erectile activity, where a significant increase was observed in all treatment groups.

Overall, the results indicate that treatment with Cordyceps militaris at appropriate doses can improve erectile activity in diabetic rats. While both Cordyceps and Viagra treatments can enhance sexual function, it is important to note that Viagra has been associated with certain adverse effects. Therefore, Cordyceps treatment may offer a potential alternative or complementary approach for improving sexual function.

Year:

2020

Link:

https://doi.org/10.1155/2020/4198397

Study type: 

Rodent study

Purpose:

To evaluate the anti-diabetic activity of Cordyceps cicadae polysaccharide in diabetic rats.

Dose:

100, 200, 400 mg/kg body weight/day of Cordyceps cicadae polysaccharide or anti-diabetic medication (glibenclamide)

Duration:

30 days

Results:

In rats, Cordyceps cicadae polysaccharide had anti-hyperglycemic effects (meaning it lowered high blood sugar), anti-hyperlipidemic effects (meaning it lowered cholesterol and triglycerides in the blood), and antioxidant effects. The highest dose of 400 mg/kg led to a 45% reduction in blood sugar levels on day 10, with a peak reduction of 73% on the 20th day. This reduction was comparable to the effect observed in rats treated with anti-diabetic medication (glibenclamide), which resulted in a 75% reduction on the 20th day. Significant reductions in blood sugar levels were also observed at doses of 100 mg/kg and 200 mg/kg.

Cordyceps cicadae polysaccharide also increased beneficial substances in the body while decreasing harmful substances. Furthermore, researchers observed a decrease in urea, creatinine, ALT (Alanine aminotransferase), AST (Aspartate aminotransferase), and ALP (Alkaline phosphatase). A decrease in these substances signifies an improvement in kidney function and liver health.

Year:

2018

Link:

https://doi.org/10.1002/cbdv.201800219