Cordyceps Mushroom (Cordyceps sinensis/militaris)

Overview

Cordyceps sinensis (now classified as Ophiocordyceps sinensis) and its cultivated relative Cordyceps militaris are entomopathogenic fungi.

Description: They parasitize insect larvae and produce a fruiting body rich in bioactive metabolites.
Historical Use: Historically used in Tibetan and Chinese medicine.
Modern Supplementation Goal: To harness these compounds for their potential to support energy metabolism, immune function, and exercise performance.

Aerobic performance & fatigue resistance: Randomized trials with 1–3 g/day of dried Cordyceps have shown modest increases in VO₂max and reduced perceived exertion in athletes (Kumar et al., 2022).
Mitochondrial and ATP support: Cordyceps supplementation improves cellular ATP production, which may translate into better endurance and reduced fatigue.
Cognitive support: Small‑scale studies report improved reaction time and mental clarity, likely linked to increased cerebral blood flow and antioxidant activity.
Metabolic regulation: Cordycepin (3‑deoxy‑adenosine) can enhance insulin sensitivity and lower fasting glucose in pre‑diabetic subjects (Wang2021).
Immune modulation: In vitro and animal data show up‑regulation of NK‑cell activity and balanced cytokine production, supporting host defense without overt inflammation.

Key Components: Cordyceps contains cordycepin, adenosine, polysaccharides (β‑glucans), and cordycepic acid (D‑mannitol).
Cordycepin Action: Cordycepin mimics adenosine, binding A₁ and A₂A receptors to modulate cAMP signaling.
- This enhances mitochondrial biogenesis via activation of AMPK and PGC‑1α pathways.
- This boosts oxidative phosphorylation and ATP synthesis.
Polysaccharide Action: Polysaccharides engage pattern‑recognition receptors (e.g., Dectin‑1) on immune cells.
- This stimulates NF‑κB‑mediated cytokine production.
- This enhances NK‑cell cytotoxicity.
Adenosine-like Moieties Action: The adenosine‑like moieties cause vasodilation via NO‑mediated endothelial relaxation, improving oxygen delivery.
Overall Effects: These actions raise energy availability, reduce oxidative stress (through up‑regulated SOD and catalase), and support immuno-metabolic homeostasis.

Standardized dried fruiting body: 1–3 g per day (split into 2–3 doses) is typical for performance and metabolic support.
Extracts (standardized to 30% cordycepin or 10% polysaccharides): 200–500 mg once or twice daily, taken with food to improve absorption.
Athlete‐specific protocols: 1 g 30 min before endurance activity may enhance acute performance; however, chronic dosing (≥4 weeks) is recommended for lasting adaptations.
Special cases:
- Lower doses (100–200 mg) are advised for elderly or those on anticoagulants.
- Higher therapeutic doses (up to 5 g/day) have been studied in fatigue‑related disorders under medical supervision.

General Tolerance: Cordyceps is generally well‑tolerated.
Common Adverse Events: Mild gastrointestinal upset (bloating, diarrhoea) is the most common adverse event.
Rare Adverse Events: Rare reports include allergic dermatitis and transient hypoglycaemia.
Contra-indications: Pregnancy, lactation, and autoimmune disease (e.g., lupus, rheumatoid arthritis) due to its immune‑stimulating effects.
Drug interactions:
- Potentiates anticoagulants (warfarin, clopidogrel) and antiplatelet agents via platelet aggregation inhibition.
- May synergize with hypoglycaemic agents (metformin, insulin) and increase risk of low blood glucose.
Caution: Individuals with severe liver or kidney disease should use caution, as high‑dose studies have shown transient liver enzyme elevations.
Recommendation: Always consult a healthcare professional before combining with prescription medication.

Hallmark Bio-active: Cordycepin (3‑deoxy‑adenosine; C₁₀H₁₃N₅O₃, IUPAC: 9‑[2‑hydroxy‑3‑(hydroxymethyl)‑4‑(hydroxymethyl)‑5‑methyl‑1‑oxopyrrol-5‑yl]‑adenine).
- It lacks the 3′‑hydroxyl group of adenosine, conferring resistance to adenosine deaminase and prolonging intracellular signaling.
Other Major Constituents:
- Cordycepic acid (D‑mannitol) – C₆H₁₄O₆
- Polysaccharides (β‑1,3/1,6‑glucans) with molecular weights 10–200 kDa
- Adenosine (C₁₀H₁₃N₅O₄) and uridine.
Properties:
- These compounds are water‑soluble, thermolabile, and exhibit moderate polarity (logP ~‑0.5 for cordycepin).
- The presence of multiple hydroxyl groups confers high solubility in aqueous extracts, while the nucleobase core enables receptor binding.

Wild O. sinensis:
- Harvested from high‑altitude grasslands of the Tibetan plateau.
- It parasitizes the larvae of Thitarodes moths.
Cultivated C. militaris:
- Most commercial products use cultivated C. militaris due to scarcity and high cost.
- Grown on sterilized grain or rice substrate.
- Controlled temperature (20‑25 °C) and humidity (70‑80 %).
Extraction Methods:
- Hot‑water extraction for polysaccharides.
- Ethanol or methanol extraction for cordycepin.
- Standardized extracts must meet ≥10 % polysaccharide or ≥30 % cordycepin content.
Quality Assurance:
- Species verification via DNA barcoding.
- Heavy‑metal (Pb, As, Cd) limits (<5 ppm).
- Microbial purity (<10³ CFU/g).
- Absence of residual solvents.
Recommendations: USDA‑GMP or ISO‑22000 certifications are recommended for reliable supplementation.