Cordyceps: Clinical Trials, Mechanism of Action, and Genetic Connections

Key takeaways:
~ Cordyceps, especially C. militaris, is used as a supplement for enhancing endurance, reducing inflammation, and modulating immune response.
~ Cordycepin is the main active compound in cordyceps.
~ It reduces inflammatory cytokines, such as IL-6 and TNF-alpha, and suppresses the NLRP3 inflammasome.

What is cordyceps, and what are the benefits of taking it as a supplement?

Cordyceps is a genus of medicinal fungi that has been used for centuries in Chinese and Tibetan medicine.[ref] More recently, cordyceps has become a popular supplement due to its performance-enhancing benefits and its role as an adaptogen that modulates the immune response.

There are multiple Cordyceps species. Two that are of interest are:

1. Cordyceps militaris (C. militaris)
2. Cordyceps sinensis (C. sinensis, now reclassified as Ophiocordyceps sinensis)

Cordyceps sinensis is the original species used in Tibet and China for centuries for energy, libido, and respiratory health. It’s a parasitic fungus that grows on the ghost moth caterpillars, high up in the Himalayas. Due to overharvesting, it’s now a threatened species, and the harvesting of it in the wild is regulated and limited. It’s a hard species to grow in artificial cultivation. [ref]

Cordyceps militaris is a related species that can be more easily cultivated on brown rice, soy, or casein as a substrate. This makes it the main species used in supplements.[ref][ref] It also has a high level of several of the beneficial compounds originally identified in C. sinensis.

Bioactive compounds in Cordyceps:

Cordycepin is the primary bioactive compound that is studied in C. militaris and C. sinensis. Cordycepin is defined as a nucleoside analog, similar to adenosine, and also known as 3′-deoxyadenosine.[ref] Nucleoside analogs are compounds that mimic the structure of the building blocks of DNA, consisting of a nucleotide plus either ribose or deoxyribose.

Because cordycepin is very similar to adenosine, it is sometimes incorporated into mRNA in place of adenosine, which leads to that mRNA not being translated into its protein. Certain mRNAs are more sensitive to cordycepin, and the effect of cordycepin on RNA polymerase is relatively minor. One protein that is affected is mTOR, and cordycepin at certain levels acts as a mild mTOR inhibitor.[ref][ref][ref]

In addition to cordycepin, C. militaris also contains “cordyceps polysaccharide, cordyceps acid, fatty acids, amino acids, vitamins, ergosterol and myriocin”.[ref]

Mechanism of Action:

Immunomodulatory and Function:

Studies show that cordyceps can help to balance and modulate the immune response, keeping it from being overactive. Researchers found that both the fruiting body and the culture mycelium extract can modulate the immune response.[ref]

In animal studies of asthma, cordyceps reduces IgE levels somewhat, but it doesn’t tamp down the immune response as much as corticosteroids do.[ref]

Modulating the immune response doesn’t just mean tamping down inflammation. It can also involve boosting the Th1 side of the immune system, which is important in fighting off pathogens, such as the flu virus. A study in healthy men showed that 1.5 g/day of C. militarus increased natural killer cell and interferon-gamma activity compared to a placebo group.[ref] Other studies in healthy adults also show that C. militarus helps to improve immune system response and boosts natural killer cell production.[ref][ref]

Anti-inflammatory function:

Cell studies using Cordyceps militaris show that it reduces the production of TNF-alpha and IL-6, which are inflammatory cytokines. Additional studies also show that it reduces the levels of  IL-1β, IL-18, IL-6, and TNF-α.[ref][ref]

The NLRP3 inflammasome increases the signal for inflammation when activated by pathogens or by damage to cells. Animal studies show that C. militaris supplementation can decrease the activation of the NLRP3 inflammasome by suppressing NF-kB. [ref]

Related article: NLRP3 inflammasome genes

In a model of acute pancreatitis, cordycepin is protective against pancreatic injury. The researchers found that cordycepin decreased inflammation (lower IL-6, IL-1β, and TNF-α) by inhibiting the activation of NF-κB and NLRP3.

Related article: Pancreatitis and Genetic Connections

Antioxidant function:

In vitro studies show that cordyceps increases the cells’ antioxidant capacity by increasing SOD1 and catalase. In addition, cordyceps also shows some non-enzymatic antioxidant properties that reduce oxidative stress without the need for upregulating glutathione.[ref][ref]

Anti-fungal:

Cordyceps also has antifungal properties. Candida albicans is an opportunistic fungal pathogen that, under the right conditions, can create a biofilm, making it difficult to control. In vitro studies also show that cordyceps can prevent Candida biofilm formation at low concentrations and help to partially eradicate mature biofilm at higher concentrations.[ref]

Conditions helped with cordyceps: Clinical trials and Research studies.

Endurance exercise:
A study in endurance athletes showed that supplementing with 2g/day of Cordyceps sinensis improved aerobic performance at 12 weeks.[ref]

Muscle growth and regeneration:
A study in healthy young athletes showed that Cordyceps sinensis supplementation at the time of intense exercise helps with stem cell recruitment to the muscles and accelerates the resolution of exercise-induced muscle damage. [ref]

Related article: Resistance Training

Respiratory capacity in exercise:

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References: