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:
- Cordyceps militaris (C. militaris)
- 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]
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
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:
A study in older adults aged 50-75 showed that taking 333 mg/3x day of Cordyceps sinensis reduced lactate levels and increased ventilatory threshold.[ref]
Asthma:
Cordyceps sinensis was compared to a placebo in patients with asthma. After three months, the Cordyceps group had decreased inflammatory markers and improved lung function and quality of life.[ref]
Related article: Asthma
Male fertility response to BPA.
Animal studies show Cordyceps can reduce the toxic effects of BPA on male testis and sperm count.[ref]
Related article: BPA
Chronic kidney disease:
A study involving patients with chronic kidney disease showed that Cordyceps militaris at 100 mg/day for three months reduces blood urea nitrogen (BUN), protein in the urine, and creatinine levels.[ref]
Epstein-Barr Virus
Cordyceps mushroom extract has been used for centuries in Chinese and Tibetan medicine. Researchers have found that cordyceps has antiviral activity against the Epstein-Barr virus and similar viruses. It downregulates most of the EBV genes and reduces extracellular and intracellular EBV concentration.[ref][ref]
Related article: Epstein-Barr virus
SARS-CoV-2 and long Covid:
A placebo-controlled clinical trial using 500mg/day of cordyceps for Covid patients showed a statistically faster recovery time (about a day faster).[ref] A preprint study showed that cordycepin from C. militaris had significant antiviral potential against SARS-CoV-2.[ref]
In long Covid patients, a clinical trial showed that C. sinensis extract improved symptoms compared to a control group.[ref]
Gouty arthritis:
A study in animals showed that Cordyceps militaris extract reduced swelling and inflammation from the uric acid crystals that cause gout.[ref]
Related article: Uric acid and gout
Klotho:
Klotho is a protein important in kidney function and in healthy longevity. Several studies show that cordyceps mushrooms may increase klotho levels.[ref] An animal study also showed that cordyceps improved Klotho protein levels in a mouse model that mimicked kidney problems.[ref]
Related article: Klotho protein
Mast cell degranulation and histamine:
Cordyceps mushroom extract has been shown in mouse models to prevent mast cell degranulation in the intestines.[ref]
Related article: Histamine intolerance, mast cell degranulation, and genetic connections
Arrhythmias:
A meta-analysis of clinical trials in China showed that cordyceps statistically improved both bradycardia and tachycardia. Importantly, no serious adverse events occurred.[ref]
Bone health:
As an analogue of adenosine, cordycepin has positive effects on bone health. Multiple animal studies show that it acts as a RANKL inhibitor and increases bone density. Researchers are also using cordyceps in studies on the regeneration of teeth and bone.[ref][ref][ref][ref] However, there are no clinical trials published on using cordyceps for osteoporosis.
Related article: Osteoporosis
Bioavailability and Metabolism of Cordyceps:
Cordyceps is readily broken down and absorbed in the intestines. However, studies show that the half-life of cordycepin, the main bioactive component, is fairly short. In rats, the half-life is around 30 minutes.[ref][ref]
Cordycepin is similar to adenosine. In the body, adenosine levels are tightly controlled, and an enzyme called adenosine deaminase (ADA) breaks down adenosine into inosine. Cordycepin is also broken down by adenosine deaminase.[ref]
Genetic variants can affect the function of the ADA gene. One variant, rs73598374, has been shown to decrease ADA activity. Theoretically, this could allow cordyceps to stay active in the body longer. However, I found no specific studies looking at the interaction between this ADA variant and cordyceps.
You can read more about the ADA variant in this article (and see your genotype below).
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| ADA | rs73598374 | T | -- | Decreased adenosine deaminase; more slow-wave sleep; groggy in the morning. |
| BDNF | rs6265 | T | -- | Decreased BDNF, averages over 20 minutes less of deep sleep |
Take it with grapefruit juice?
Inhibiting adenosine deaminase can increase the time that cordycepin is available. Naringin, a flavonoid found in citrus fruit and most abundant in grapefruit, inhibits adenosine deaminase.[ref]
Cautions:
Talk with your doctor if you have any questions on whether cordyceps is right for you. Be sure to check on interactions with medications. For example, animal studies show that cordyceps blocks the absorption of cyclosporin, an antibiotic, when taken orally.[ref]
While there are no known overdose or toxic risks with cordyceps, be sure to seek a high-quality supplement that isn’t contaminated with arsenic or heavy metals.[ref]
Ergothionine Genetic Interaction:
Cordyceps mushroom fruiting body extract does contain ergothionine, which is an antioxidant found in many types of mushrooms.[ref] For people with IBD and certain genetic variants (below), ergothionine can exacerbate intestinal problems. (Full article on Ergothionine and IBD here)
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| SLC22A4 | rs1050152 | T | -- | Likely to be intolerant of ergothioneine (in mushrooms) with IBD |
Who might Cordyceps work best for?
This section is speculative, but I wanted to draw some connections between genetic variants and the effects of cordyceps in studies.
TNF-alpha variants that increase inflammation may be helped by cordyceps. Read the full article on TNF here.
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| TNF | rs1800629 | A | -- | Increased TNF alpha, increased risk of many chronic inflammatory diseases |
| TNF | rs361525 | A | -- | Increased TNF alpha, increased risk of many chronic inflammatory diseases |
| TNF | rs1799964 | C | -- | Increased TNF alpha, increased risk of many chronic inflammatory diseases |
| TNF | rs1799724 | T | -- | Increased TNF alpha, increased risk of many chronic inflammatory diseases |
| TNFRSF1A | rs1800693 | C | -- | Increased risk of multiple sclerosis; increased NF-kB signaling |
| TNFRSF1A | rs767455 | C | -- | Increased risk of inflammatory diseases. |
| TNFRSF1B | rs1061622 | G | -- | Increased risk of psoriasis, lupus |
| TNF | rs1800610 | A | -- | Lower TNF; less inflammation but more susceptible to infectious diseases |
NLRP3 genetic variants can increase overall inflammation through easier activation of the inflammasome. Read the full article on NLRP3 here.
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| CIAS1 | rs35829419 | A | -- | Increased NLRP3 activation |
| CIAS1 | rs1539019 | A | -- | AA only: Increased NLRP3 |
| CIAS1 | rs10754558 | C | -- | Somewhat increased NLRP3 activation |
| CIAS1 | rs3806265 | C | -- | Somewhat increased NLRP3 activation |
| CIAS1 | rs10733113 | A | -- | Somewhat increased NLRP3 activation |
| CIAS1 | rs12048215 | G | -- | Somewhat increased NLRP3 activation |
| CIAS1 | i5007539 | G | -- | Carrier of a mutation linked to familial cold urticaria |
| CIAS1 | rs28937896 | C | -- | Carrier of a mutation linked to familial cold urticaria |
| CIAS1 | rs121908147 | A | -- | Carrier of a mutation linked to familial cold urticaria |
| CIAS1 | rs121908150 | T | -- | Carrier of a mutation linked to familial cold urticaria |
| CIAS1 | rs121908148 | G | -- | Carrier of a mutation linked to familial cold urticaria |
| CIAS1 | i6015531 | A | -- | Increased NLRP3 activation |
| CIAS1 | rs7525979 | T | -- | increased risk of cognitive impairment in aging; increased risk of gouty arthritis (TT only) |
| CIAS1 | rs4925648 | T | -- | increased risk of asthma; TT- increased risk of Crohn's |
Asthma has traditionally been treated in Chinese medicine with cordyceps. At least part of the connection here is through decreasing mast cell activation and by tamping down inflammation. People with asthma should talk with their doctor about any supplement before starting something new. Read the full article on asthma here.
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| TSLP | rs3806932 | G | -- | increased relative risk of childhood allergic asthma and adult-onset asthma |
| TSLP | rs1837253 | T | -- | Decreased risk of adult asthma (good) |
| IL4 | rs2243250 | T | -- | increased relative risk of asthma |
| IL33 | rs928413 | G | -- | increased risk of asthma, allergies, and COPD |
| IL33 | rs7037276 | C | -- | increased relative risk of asthma |
| IL33 | rs1342326 | C | -- | increased relative risk of asthma |
| IL33 | rs3939286 | T | -- | increased relative risk of asthma |
| TBX21 | rs4794067 | C | -- | increased risk of aspirin-induced asthma, increased risk of asthma in children |
| TBX21 | rs11650354 | C | -- | increased risk of asthma |
| IL17A | rs2275913 | A | -- | Higher IL17A, Increased risk of inflammatory diseases including periodontitis, inflammatory bowel disease, asthma; 3-fold increased risk of COPD (smokers) |
| IL17A | rs279548 | T | -- | somewhat increased IL17A, increased risk of asthma |
| TNF | rs1800629 | A | -- | Higher TNF-alpha levels. Increased risk of asthma and COPD |
| TNF | rs361525 | A | -- | higher TNF-alpha levels, increased risk of asthma, COPD |
| IFNG | rs2069705 | A | -- | A/A: increased relative risk of asthma; A/G: typical |
| ILIR1 | rs3771166 | A | -- | Decreased risk of asthma |
| NLRP3 | rs10754558 | C | -- | higher inflammation, increased relative risk of asthma |
| IL13 | rs20541 | A | -- | higher IgE levels; higher risk of allergies, increased risk of COPD, increased dust mite allergies increased risk of asthma |
| IL13 | rs1295686 | T | -- | increased risk of asthma |
| IL13 | rs1800925 | T | -- | increased IgE levels; increased risk of asthma; increased risk of periodontitis, increased risk of COPD |
| IL13 | rs848 | A | -- | increased risk of asthma, increased risk of alopecia areata |
| HNMT | rs2071048 | T | -- | increased risk of asthma (and higher histamine), common variant |
| HRH1 | rs901865 | T | -- | increased asthma risk (likely increase HRH1) |
| MTHFR | rs1801133 | A | -- | two copies of MTHFR C677T, enzyme function decreased by 70 – 80%, increased relative risk of asthma |
| GSTA1 | rs3957357 | A | -- | low/ non-functioning enzyme; increased risk of asthma, allergies |
| GSTP1 | rs1138272 | T | -- | Increased risk of asthma and exacerbations with higher air pollution exposure |
| GSDMB | rs7216389 | T | -- | Increased risk of childhood asthma 3-fold increased risk of asthma with known mold exposure |
| GSDMB | rs2305480 | G | -- | increased risk of asthma, especially with cigarette smoke exposure |
| SOD2 | rs5746136 | T | -- | higher phthalate metabolite levels, almost 3-fold increased risk of asthma |
| CDHR3 | rs6967330 | A | -- | higher levels of CDHR3, increased risk of rhinovirus infections and severe asthma in children |
| ADRB2 | rs1042713 | A | -- | more likely to have poor response to long-acting β2-agonist (LABA), increased exacerbations in children treated with LABAs plus inhaled corticosteroids (but not corticosteroids alone) |
| ARG1 | rs2781659 | G | -- | lower acute response to inhaled beta-agonists in children with asthma |
| HNMT | rs11558538 | T | -- | reduced HNMT activity, higher histamine levels, increased relative risk of asthma |
| HNMT | i3000469 | T | -- | reduced HNMT activity, higher histamine levels, increased relative risk of asthma |
| HLA-DQ | rs9273349 | C | -- | increased relative risk of asthma |